US20020119177A1 - Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration - Google Patents
Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration Download PDFInfo
- Publication number
- US20020119177A1 US20020119177A1 US09/747,488 US74748800A US2002119177A1 US 20020119177 A1 US20020119177 A1 US 20020119177A1 US 74748800 A US74748800 A US 74748800A US 2002119177 A1 US2002119177 A1 US 2002119177A1
- Authority
- US
- United States
- Prior art keywords
- implant
- component
- tissue
- foam
- mesh
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/48—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with macromolecular fillers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/24—Structurally defined web or sheet [e.g., overall dimension, etc.]
- Y10T428/24149—Honeycomb-like
Definitions
- the present invention relates to bioabsorbable, porous, reinforced, biocompatible tissue repair stimulating implant devices comprising at least one biological component for use in the repair of orthopaedic type injuries, such as damage to the meniscus and rotator cuff, and methods for making such devices.
- tissue such as cartilage, muscle, bone, and sinew that requires repair by surgical intervention.
- repairs can be effected by suturing or otherwise repairing the damaged tissue, and/or by augmenting the damaged tissue with other tissue or with a tissue implant.
- the implant can provide structural support to the damaged tissue.
- a common tissue injury concerns damage to cartilage, for example, the menisci of a knee joint.
- menisci of the knee joint There are two menisci of the knee joint, a medial and a lateral meniscus.
- the meniscus is a biconcave, fibrocartilage tissue that is interposed between the femur and tibia of the leg.
- the primary functions of the meniscus are to bear loads, absorb shock, stabilize, and lubricate the joint. If not treated properly, an injury to the meniscus, such as a “bucket-handle tear,” can lead to the development of osteoarthritis.
- treatment modalities for a damaged meniscus include removal of the meniscus and surgical repair of the damaged meniscus.
- Another common tissue injury is a damaged or torn rotator cuff, which facilitates circular motion of the humerus bone relative to the scapula.
- the most common injury associated with the rotator cuff is a strain or tear to the supraspinatus tendon. This tear can be at the insertion site of the tendon with the humerus, thereby releasing the tendon partially, or fully (depending upon the severity of the injury), from the bone. Additionally, the strain or tear can occur within the tendon itself. Treatment for a strained tendon usually involves physical cessation from use of the tendon.
- a torn tendon might require surgical intervention as in the case of a full tear of the supraspinatus tendon from the humerus.
- Surgical intervention can involve the repair and/or reattachment of torn tissue.
- a prolonged recovery period often follows repair of a rotator cuff tear.
- Surgical treatment of damaged tissue would benefit from techniques that effect a more reliable repair of tissue, and which facilitate more rapid healing.
- various implants have been used in surgical procedures to help achieve these benefits.
- implants include those that are made from biologically derived tissue (e.g., allografts and autografts), and those that are synthetic.
- biologically derived tissue e.g., allografts and autografts
- synthetic materials can have disadvantages in that they can contribute to disease transmission, while synthetic materials are difficult to manufacture in such a way that their properties are reproducible from batch to batch.
- This invention relates to bioabsorbable, porous, reinforced, biocompatible tissue repair stimulating implant, or “scaffold,” devices for use in the repair and/or regeneration of diseased or damaged tissue, and the methods for making and using these devices.
- the implants comprise a bioabsorable polymeric foam component having pores with an open cell pore structure.
- the foam component is reinforced with a material such as a mesh.
- the implant has sufficient structural integrity to enable it to be handled in the operating room prior to and during implantation.
- These implants should also have sufficient properties (e.g., tear strength) to enable them to accept and retain sutures or other fasteners without tearing. Desirable properties are imparted to the implant of the invention by integrating the foam component with the reinforcement component.
- the implant may include one or more layers of each of the foam and reinforcement components. Preferably, adjacent layers of foam are also integrated by at least a partial interlocking of the pore-forming webs or walls in the adjacant layers.
- the implants of the instant invention further comprise at least one biological component that is incorporated therein.
- the reinforcement material is preferably a mesh, which may be bioabsorbable.
- the reinforcement should have a sufficient mesh density to permit suturing, but the density should not be so great as to impede proper bonding between the foam and the reinforcement.
- a preferred mesh density is in the range of about 12 to 80%.
- the biological component of the present invention comprises at least one effector molecule and/or cell, which contributes to the healing process of an injured tissue. Collectively, these materials are sometimes referred to herein as “effectors.”
- the effectors can be a cellular factor such as a protein or peptide (for the sake of simplicity, use of the term “protein” herein will include peptide), a non-protein biomolecule, a cell type, a pharmaceutical agent, or combinations thereof.
- One function of the implant of the current invention is as a carrier for the effectors, and the effector can be incorporated within the implant either prior to or following surgical placement of the implant.
- FIG. 1 is a sectional view of a tissue implant constructed according to the present invention
- FIG. 2 is a sectional view of an alternative embodiment of the implant of the present invention.
- FIG. 3 is a sectional view of yet another embodiment of the implant of the present invention.
- FIG. 4 is a perspective view of one embodiment of a mold set-up useful with the present invention.
- FIG. 5 is a sectional view of a portion of the mold set-up of FIG. 4;
- FIG. 6 is a scanning electron micrograph of a bioabsorbable knitted mesh reinforcement material useful with the implant of the present invention.
- FIG. 7 is a scanning electron micrograph of a portion of an implant according to the present invention.
- the present invention relates to a biocompatible tissue repair stimulating implant or “scaffold” device which, preferably, is bioabsorbable, and to methods for making and using such a device.
- the implant includes one or more layers of a bioabsorbable polymeric foam having pores with an open cell pore structure.
- a reinforcement component is also present within the implant to contribute enhanced mechanical and handling properties.
- the reinforcement component is preferably in the form of a mesh fabric that is biocompatible.
- the reinforcement component may be bioabsorbable as well.
- the implant has incorporated therein a biological component, or effector that assists in and/or expedites tissue healing.
- the biological component is housed primarily within the pores of the foam component of the implant.
- tissue implants of the invention In some surgical applications, such as for use in the repair of a torn rotator cuff or meniscus, the tissue implants of the invention must be able to be handled in the operating room, and they must be able to be sutured or otherwise fastened without tearing. Additionally, the implants should have a burst strength adequate to reinforce the tissue, and the structure of the implant must be suitable to encourage tissue ingrowth.
- a preferred tissue ingrowth-promoting structure is one where the cells of the foam component are open and sufficiently sized to permit cell ingrowth and to house the effector.
- a suitable pore size to accommodate these features is one in which the pores have an average diameter in the range of about 100 to 1000 microns and, more preferably, about 150 to 500 microns.
- the implant 10 includes a polymeric foam component 12 and a reinforcement component 14 .
- the foam component preferably has pores 13 with an open cell pore structure.
- the reinforcement material can be disposed at any location within the implant.
- more than one layer of each of the foam component 12 a , 12 b and reinforcement component 14 a , 14 b may be present in the implant. It is understood that various layers of the foam component and/or the reinforcement materials may be made from different materials and have different pore sizes.
- FIG. 3 illustrates an embodiment in which a barrier layer 16 is present in the implant. Although illustrated as being only on one surface of the implant 10 , the barrier layer 16 may be present on either or both of the top and bottom surfaces 18 , 20 of the implant.
- the implant 10 must have sufficient structural integrity and physical properties to facilitate ease of handling in an operating room environment, and to permit it to accept and retain sutures or other fasteners without tearing. Adequate strength and physical properties are developed in the implant through the selection of materials used to form the foam and reinforcement components, and the manufacturing process. As shown in FIG. 7, the foam component 12 is integrated with the reinforcement component 14 such that the web or walls of the foam componenets that form pores 13 penetrate the mesh of the reinforcement component 14 and interlock with the reinforcement component. The pore-forming walls in adjacent layers of the foam component also interlock with one another, regardless of whether the foam layers are separated by a layer of reinforcement materials or whether they are made of the same or different materials.
- bioabsorbable polymers can be used to make porous, reinforced tissue repair stimulating implant or scaffold devices according to the present invention.
- suitable biocompatible, bioabsorbable polymers include polymers selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, tyrosine derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, biomolecules (i.e., biopolymers such as collagen, elastin, bioabsorbable starches, etc.) and blends thereof.
- aliphatic polyesters include, but are not limited to, homopolymers and copolymers of lactide (which includes lactic acid, D-,L- and meso lactide), glycolide (including glycolic acid), ⁇ -caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, ⁇ -valerolactone, ⁇ -butyrolactone, ⁇ -butyrolactone, ⁇ -decalactone, hydroxybutyrate, hydroxyvalerate, 1 ,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6 -dimethyl-1,4-dioxan-2-one 2,5-diketomorpholine, pival
- Poly(iminocarbonates), for the purpose of this invention are understood to include those polymers as described by Kemnitzer and Kohn, in the Handbook of Biodegradable Polymers , edited by Domb, et. al., Hardwood Academic Press, pp. 251-272 (1997).
- Copoly(ether-esters), for the purpose of this invention are understood to include those copolyester-ethers as described in the Journal of Biomaterials Research, Vol. 22, pages 993-1009, 1988 by Cohn and Younes, and in Polymer Preprints (ACS Division of Polymer Chemistry), Vol. 30(1), page 498 , 1989 by Cohn (e.g., PEO/PLA).
- Polyalkylene oxalates for the purpose of this invention, include those described in U.S. Pat. Nos. 4,208,511; 4,141,087; 4,130,639; 4,140,678; 4,105,034; and 4,205,399.
- Polyphosphazenes, co-, ter- and higher order mixed monomer based polymers made from L-lactide, D,L-lactide, lactic acid, glycolide, glycolic acid, para-dioxanone, trimethylene carbonate and E-caprolactone such as are described by Allcock in The Encyclopedia of Polymer Science , Vol.
- Polyanhydrides include those derived from diacids of the form HOOC—C 6 H 4—O-(CH 2 ) m —O—C 6 H 4 —COOH, where “m” is an integer in the range of from 2 to 8, and copolymers thereof with aliphatic alpha-omega diacids of up to 12 carbons.
- Polyoxaesters, polyoxaamides and polyoxaesters containing amines and/or amido groups are described in one or more of the following U.S. Pat. Nos. 5,464,929; 5,595,751; 5,597,579; 5,607,687; 5,618,552; 5,620,698; 5,645,850; 5,648,088; 5,698,213; 5,700,583; and 5,859,150.
- Polyorthoesters such as those described by Heller in Handbook of Biodegradable Polymers , edited by Domb, et al., Hardwood Academic Press, pp. 99-118 (1997).
- glycol is understood to include polyglycolic acid.
- lactide is understood to include L-lactide, D-lactide, blends thereof, and lactic acid polymers and copolymers.
- aliphatic polyesters are among the preferred absorbable polymers for use in making the foam implants according to the present invention.
- Aliphatic polyesters can be homopolymers, copolymers (random, block, segmented, tapered blocks, graft, triblock, etc.) having a linear, branched or star structure.
- Suitable monomers for making aliphatic homopolymers and copolymers may be selected from the group consisting of, but are not limited, to lactic acid, lactide (including L-, D-, meso and D,L mixtures), glycolic acid, glycolide, ⁇ -caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3 -dioxan-2-one), ⁇ -valerolactone, ⁇ -butyrolactone, ⁇ -decalactone, 2,5-diketomorpholine, pivalolactone, ⁇ , ⁇ -diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4 -dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, ⁇ -butyrolactone, 1,4-dioxepan-2-one, 1,5
- Elastomeric copolymers are also particularly useful in the present invention.
- Suitable elastomeric polymers include those with an inherent viscosity in the range of about 1.2 dL/g to 4 dL/g, more preferably about 1.2 dL/g to 2 dL/g and most preferably about 1.4 dL/g to 2 dL/g as determined at 25° C. in a 0.1 gram per deciliter (g/dL) solution of polymer in hexafluoroisopropanol (HFIP).
- suitable elastomers exhibit a high percent elongation and a low modulus, while possessing good tensile strength and good recovery characteristics.
- the elastomer from which the foam component is formed exhibits a percent elongation (e.g., greater than about 200 percent and preferably greater than about 500 percent).
- suitable elastomers should also have a tensile strength greater than about 500 psi, preferably greater than about 1,000 psi, and a tear strength of greater than about 50 lbs/inch, preferably greater than about 80 lbs/inch.
- Exemplary bioabsorbable, biocompatible elastomers include, but are not limited to, elastomeric copolymers of ⁇ -caprolactone and glycolide (including polyglycolic acid) with a mole ratio of ⁇ -caprolactone to glycolide of from about 35:65 to about 65:35, more preferably from 45:55 to 35:65; elastomeric copolymers of ⁇ -caprolactone and lactide (including L-lactide, D-lactide, blends thereof, and lactic acid polymers and copolymers) where the mole ratio of ⁇ -caprolactone to lactide is from about 35:65 to about 65:35 and more preferably from 45:55 to 30:70 or from about 95:5 to about 85:15; elastomeric copolymers of p-dioxanone (1,4-dioxan-2-one) and lactide (including L-lactide, D-lactide, blends thereof
- the elastomer is a 35:65 copolymer of polyglycolic acid and polycaprolactone, formed in a dioxane solvent and including a polydioxanone mesh.
- the elastomer is a 50:50 blend of a 35:65 copolymer of polyglycolic acid and polycaprolactone and 40:60 ⁇ -caprolactone-co-lactide.
- a suitable polymer or copolymer for forming the foam depends on several factors.
- the more relevant factors in the selection of the appropriate polymer(s) that is used to form the foam component include bioabsorption (or bio-degradation) kinetics; in vivo mechanical performance; cell response to the material in terms of cell attachment, proliferation, migration and differentiation; and biocompatibility.
- Other relevant factors, which to some extent dictate the in vitro and in vivo behavior of the polymer include the chemical composition, spatial distribution of the constituents, the molecular weight of the polymer, and the degree of crystallinity.
- the ability of the material substrate to resorb in a timely fashion in the body environment is critical. But the differences in the absorption time under in vivo conditions can also be the basis for combining two different copolymers.
- a copolymer of 35:65 ⁇ -caprolactone and glycolide (a relatively fast absorbing polymer) is blended with 40:60 ⁇ -caprolactone and L-lactide copolymer (a relatively slow absorbing polymer) to form a foam component.
- the two constituents can be either randomly inter-connected bicontinuous phases, or the constituents could have a gradient-like architecture in the form of a laminate type composite with a well integrated interface between the two constituent layers.
- the microstructure of these foams can be optimized to regenerate or repair the desired anatomical features of the tissue that is being engineered.
- polymer blends to form structures which transition from one composition to another composition in a gradient-like architecture.
- Foams having this gradient-like architecture are particularly advantageous in tissue engineering applications to repair or regenerate the structure of naturally occurring tissue such as cartilage (articular, meniscal, septal, tracheal, etc.), rotator cuff, esophagus, skin, bone, and vascular tissue.
- a foam may be formed that transitions from a softer spongy material to a stiffer more rigid material in a manner similar to the transition from cartilage to bone.
- a foam may be used for similar gradient effects, or to provide different gradients (e.g., different absorption profiles, stress response profiles, or different degrees of elasticity).
- such design features can establish a concentration gradient for the biological component or effector such that a higher concentration of the effector is present in one region of the implant (e.g., an interior portion) than in another region (e.g., outer portions).
- a concentration gradient for the biological component or effector such that a higher concentration of the effector is present in one region of the implant (e.g., an interior portion) than in another region (e.g., outer portions).
- This may be effected by engineering an implant in which the overall pore volume is greater in a region in which it is desired to have a greater concentration of biological component.
- the implants of the invention can also be used for organ repair replacement or regeneration strategies that may benefit from these unique tissue implants.
- these implants can be used for spinal disc, cranial tissue, dura, nerve tissue, liver, pancreas, kidney, bladder, spleen, cardiac muscle, skeletal muscle, skin, fascia, maxillofacial, stomach, tendons, cartilage, ligaments, and breast tissues.
- the reinforcing component of the tissue repair stimulating implant of the present invention can be comprised of any absorbable or non-absorbable biocompatible material, including textiles with woven, knitted, warped knitted (i.e., lace-like), non-woven, and braided structures.
- the reinforcing component has a mesh-like structure.
- mechanical properties of the material can be altered by changing the density or texture of the material, or by embedding particles in the material.
- the fibers used to make the reinforcing component can be monofilaments, yams, threads, braids, or bundles of fibers.
- fibers can be made of any biocompatible material including bioabsorbable materials such as polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polydioxanone (PDO), trimethylene carbonate (TMC), polyvinyl alcohol (PVA), copolymers or blends thereof.
- PLA polylactic acid
- PGA polyglycolic acid
- PCL polycaprolactone
- PDO polydioxanone
- TMC trimethylene carbonate
- PVA polyvinyl alcohol copolymers or blends thereof.
- the fibers are formed of a polylactic acid and polyglycolic acid copolymer at a 95:5 mole ratio.
- the fibers that form the reinforcing material can be made of a bioabsorbable glass.
- Bioglass, a silicate containing calcium phosphate glass, or calcium phosphate glass with varying amounts of solid particles added to control resorption time are examples of materials that could be spun into glass fibers and used for the reinforcing material.
- Suitable solid particles that may be added include iron, magnesium, sodium, potassium, and combinations thereof.
- the reinforcing material may also be formed from a thin, perforation-containing elastomeric sheet with perforations to allow tissue ingrowth.
- a thin, perforation-containing elastomeric sheet with perforations to allow tissue ingrowth.
- Such a sheet could be made of blends or copolymers of polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), and polydioxanone (PDO).
- filaments that form the reinforcing material may be co-extruded to produce a filament with a sheath/core construction.
- Such filaments are comprised of a sheath of biodegradable polymer that surrounds one or more cores comprised of another biodegradable polymer. Filaments with a fast-absorbing sheath surrounding a slower-absorbing core may be desirable in instances where extended support is necessary for tissue ingrowth.
- one or more layers of the reinforcing material may be used to reinforce the tissue implant of the invention.
- biodegradable reinforcing layers e.g., meshes
- biodegradable reinforcing layers e.g., meshes
- the same structure and chemistry or different structures and chemistries can be overlaid on top of one another to fabricate reinforced tissue implants with superior mechanical strength.
- the biological component that is incorporated within the implant can be selected from among a variety of effectors that, when present at the site of injury, promote healing and/or regeneration of the affected tissue.
- the effectors may also include compounds or agents that prevent infection (e.g., antimicrobial agents and antibiotics), compounds or agents that reduce inflammation (e.g., anti-inflammatory agents), and compounds or agents that suppress the immune system (e.g., immunosuppressants).
- effectors present within the implant of the present invention include heterologous or autologous growth factors, proteins, glycoproteins, hormones, cytokines, glycosaminoglycans, nucleic acids, analgesics, and cell types. It is understood that one or more effectors of the same or different functionality may be incorporated within the implant.
- suitable effectors include the multitude of heterologous or autologous growth factors known to promote healing and/or regeneration of injured or damaged tissue.
- Exemplary growth factors include, but are not limited to, TGF-P, bone morphogenic protein, fibroblast growth factor, platelet-derived growth factor, vascular endothelial cell-derived growth factor (VEGF), epidermal growth factor, insulin-like growth factor, hepatocyte growth factor, and fragments thereof.
- the proteins that may be present within the implant include proteins that are secreted from a cell which is housed within the implant, as well as those that are present within the implant in an isolated form.
- the isolated form of a protein typically is one that is about 55% or greater in purity, i.e., isolated from other cellular proteins, molecules, debris, etc. More preferably, the isolated protein is one that is at least 65% pure, and most preferably one that is at least about 75 to 95% pure. Notwithstanding the above, one of ordinary skill in the art will appreciate that proteins having a purity below about 55% are still considered to be within the scope of this invention.
- protein embraces glycoproteins, lipoproteins, proteoglycans, peptides, and fragments thereof.
- proteins useful as effectors include, but are not limited to, pleiotrophin, endothelin, tenascin, fibronectin, fibrinogen, vitronectin, V-CAM, I-CAM, N-CAM, selectin, cadherin, integrin, laminin, actin, myosin, collagen, microfilament, intermediate filament, antibody, elastin, fibrillin, and fragments thereof.
- Glycosaminoglycans may also serve as effectors according to the present invention.
- Exemplary glycosaminoglycans useful as effectors include, but are not limited to, heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate, keratin sulfate, hyaluronan (also known as hyaluronic acid), and combinations thereof.
- Suitable cell types that can serve as effectors according to this invention include, but are not limited to, osteocytes, osteoblasts, osteoclasts, fibroblasts, stem cells, pluripotent cells, chondrocyte progenitors, chondrocytes, endothelial cells, macrophages, leukocytes, adipocytes, monocytes, plasma cells, mast cells, umbilical cord cells, stromal cells, mesenchymal stem cells, epithelial cells, myoblasts, and bone marrow cells.
- Cells typically have at their surface receptor molecules which are responsive to a cognate ligand (e.g., a stimulator).
- a stimulator is a ligand which when in contact with its cognate receptor induce the cell possessing the receptor to produce a specific biological action.
- a cell may produce significant levels of secondary messengers, like Ca +2 , which then will have subsequent effects upon cellular processes such as the phosphorylation of proteins, such as (keeping with our example) protein kinase C.
- secondary messengers like Ca +2
- proteins such as (keeping with our example) protein kinase C.
- the cell secretes a cellular messenger usually in the form of a protein (including glycoproteins, proteoglycans, and lipoproteins).
- This cellular messenger can be an antibody (e.g., secreted from plasma cells), a hormone, (e.g., a paracrine, autocrine, or exocrine hormone), or a cytokine.
- the foam component of the tissue implant may be formed as a foam by a variety of techniques well known to those having ordinary skill in the art.
- the polymeric starting materials may be foamed by lyophilization, supercritical solvent foaming (i.e., as described in EP 464,163), gas injection extrusion, gas injection molding or casting with an extractable material (e.g., salts, sugar or similar suitable materials).
- the foam component of the engineered tissue repair stimulating implant devices of the present invention may be made by a polymer-solvent phase separation technique, such as lyophilization.
- a polymer solution can be separated into two phases by any one of the four techniques: (a) thermally induced gelation/crystallization; (b) non-solvent induced separation of solvent and polymer phases; (c) chemically induced phase separation, and (d) thermally induced spinodal decomposition.
- the polymer solution is separated in a controlled manner into either two distinct phases or two bicontinuous phases. Subsequent removal of the solvent phase usually leaves a porous structure of density less than the bulk polymer and pores in the micrometer ranges. See Microcellular Foams Via Phase Separation, J. Vac. Sci. Technolol., A. T. Young, Vol. 4(3), May/Jun 1986.
- the steps involved in the preparation of these foams include choosing the right solvents for the polymers to be lyophilized and preparing a homogeneous solution.
- the polymer solution is subjected to a freezing and vacuum drying cycle.
- the freezing step phase separates the polymer solution and vacuum drying step removes the solvent by sublimation and/or drying, leaving a porous polymer structure or an interconnected open cell porous foam.
- Suitable solvents that may be used in the preparation of the foam component include, but are not limited to, formic acid, ethyl formate, acetic acid, hexafluoroisopropanol (HFIP), cyclic ethers (e.g., tetrahydrofuran (THF), dimethylene fluoride (DMF), and polydioxanone (PDO)), acetone, acetates of C2 to C5 alcohols (e.g., ethyl acetate and t-butylacetate), glyme (e.g., monoglyme, ethyl glyme, diglyme, ethyl diglyme, triglyme, butyl diglyme and tetraglyme), methylethyl ketone, dipropyleneglycol methyl ether, lactones (e.g., ⁇ -valerolactone, ⁇ -valerolactone, ⁇ -
- the applicable polymer concentration or amount of solvent that may be utilized will vary with each system. Generally, the amount of polymer in the solution can vary from about 0.5% to about 90% and, preferably, will vary from about 0.5% to about 30% by weight, depending on factors such as the solubility of the polymer in a given solvent and the final properties desired in the foam.
- solids may be added to the polymer-solvent system to modify the composition of the resulting foam surfaces. As the added particles settle out of solution to the bottom surface, regions will be created that will have the composition of the added solids, not the foamed polymeric material. Alternatively, the added solids may be more concentrated in desired regions (i.e., near the top, sides, or bottom) of the resulting tissue implant, thus causing compositional changes in all such regions. For example, concentration of solids in selected locations can be accomplished by adding metallic solids to a solution placed in a mold made of a magnetic material (or vice versa).
- a variety of types of solids can be added to the polymer-solvent system.
- the solids are of a type that will not react with the polymer or the solvent.
- the added solids have an average diameter of less than about 1.0 mm and preferably will have an average diameter of about 50 to about 500 microns.
- the solids are present in an amount such that they will constitute from about 1 to about 50 volume percent of the total volume of the particle and polymer-solvent mixture (wherein the total volume percent equals 100 volume percent).
- Exemplary solids include, but are not limited to, particles of demineralized bone, calcium phosphate particles, Bioglass particles, calcium sulfate, or calcium carbonate particles for bone repair, leachable solids for pore creation and particles of bioabsorbable polymers not soluble in the solvent system that are effective as reinforcing materials or to create pores as they are absorbed, and non-bioabsorbable materials.
- Suitable leachable solids include nontoxic leachable materials such as salts (e.g., sodium chloride, potassium chloride, calcium chloride, sodium tartrate, sodium citrate, and the like), biocompatible mono and disaccharides (e.g., glucose, fructose, dextrose, maltose, lactose and sucrose), polysaccharides (e.g., starch, alginate, chitosan), water soluble proteins (e.g., gelatin and agarose).
- salts e.g., sodium chloride, potassium chloride, calcium chloride, sodium tartrate, sodium citrate, and the like
- biocompatible mono and disaccharides e.g., glucose, fructose, dextrose, maltose, lactose and sucrose
- polysaccharides e.g., starch, alginate, chitosan
- water soluble proteins e.g., gelatin and agarose
- the leachable materials can be removed by immersing the foam with the leachable material in a solvent in which the particle is soluble for a sufficient amount of time to allow leaching of substantially all of the particles, but which does not dissolve or detrimentally alter the foam.
- the preferred extraction solvent is water, most preferably distilled-deionized water.
- the foam will be dried after the leaching process is complete at low temperature and/or vacuum to minimize hydrolysis of the foam unless accelerated absorption of the foam is desired.
- Suitable non-bioabsorbable materials include biocompatible metals such as stainless steel, cobalt chrome, titanium and titanium alloys, and bioinert ceramic particles (e.g., alumina, zirconia, and calcium sulfate particles).
- non-bioabsorbable materials may include polymers such as polyethylene, polyvinylacetate, polymethylmethacrylate, silicone, polyethylene oxide, polyethylene glycol, polyurethanes, polyvinyl alcohol, natural biopolymers (e.g., cellulose particles, chitin, keratin, silk, and collagen particles), and fluorinated polymers and copolymers (e.g., polyvinylidene fluoride, polytetrafluoroethylene, and hexafluoropropylene).
- polymers such as polyethylene, polyvinylacetate, polymethylmethacrylate, silicone, polyethylene oxide, polyethylene glycol, polyurethanes, polyvinyl alcohol, natural biopolymers (e.g., cellulose particles, chitin, keratin, silk, and collagen particles), and fluorinated polymers and copolymers (e.g., polyvinylidene fluoride, polytetrafluoroethylene, and hexafluoro
- solids e.g., barium sulfate
- the solids that may be added also include those that will promote tissue regeneration or regrowth, as well as those that act as buffers, reinforcing materials or porosity modifiers.
- porous, reinforced tissue repair stimulating implant devices of the present invention are made by injecting, pouring, or otherwise placing, the appropriate polymer solution into a mold set-up comprised of a mold and the reinforcing elements of the present invention.
- the mold set-up is cooled in an appropriate bath or on a refrigerated shelf and then lyophilized, thereby providing a reinforced tissue engineered scaffold.
- the biological component can be added either before or after the lyophilization step. In the course of forming the foam component, it is believed to be important to control the rate of freezing of the polymer-solvent system.
- the type of pore morphology that is developed during the freezing step is a function of factors such as the solution thermodynamics, freezing rate, temperature to which it is cooled, concentration of the solution, and whether homogeneous or heterogenous nucleation occurs.
- factors such as the solution thermodynamics, freezing rate, temperature to which it is cooled, concentration of the solution, and whether homogeneous or heterogenous nucleation occurs.
- the required general processing steps include the selection of the appropriate materials from which the polymeric foam and the reinforcing components are made. If a mesh reinforcing material is used, the proper mesh density must be selected. Further, the reinforcing material must be properly aligned in the mold, the polymer solution must be added at an appropriate rate and, preferably, into a mold that is tilted at an appropriate angle to avoid the formation of air bubbles, and the polymer solution must be lyophilized.
- the reinforcing mesh has to be of a certain density. That is, the openings in the mesh material must be sufficiently small to render the construct sutureable or otherwise fastenable, but not so small as to impede proper bonding between the foam and the reinforcing mesh as the foam material and the open cells and cell walls thereof penetrate the mesh openings. Without proper bonding the integrity of the layered structure is compromised leaving the construct fragile and difficult to handle.
- the reinforcement material is substantially flat when placed in the mold.
- the reinforcement e.g., mesh
- the reinforcement is pressed flat using a heated press prior to its placement within the mold.
- marking the construct can be accomplished by embedding one or more indicators, such as dyed markings or dyed threads, within the woven reinforcements. The direction or orientation of the indicator will indicate to a surgeon the dimension of the implant in which physical properties are superior.
- the manner in which the polymer solution is added to the mold prior to lyophilization helps contribute to the creation of a tissue implant with adequate mechanical integrity.
- a mesh reinforcing material will be used, and that it will be positioned between two thin (e.g., 0.75 mm)
- shims it should be positioned in a substantially flat orientation at a desired depth in the mold.
- the polymer solution is poured in a way that allows air bubbles to escape from between the layers of the foam component.
- the mold is tilted at a desired angle and pouring is effected at a controlled rate to best prevent bubble formation.
- the mold is tilted at a desired angle and pouring is effected at a controlled rate to best prevent bubble formation.
- the rate of pouring should be slow enough to enable any air bubbles to escape from the mold, rather than to be trapped in the mold.
- a mesh material is used as the reinforcing component, the density of the mesh openings is an important factor in the formation of a resulting tissue implant with the desired mechanical properties.
- a low density, or open knitted mesh material is preferred.
- One particularly preferred material is a 90/10 copolymer of PGA/PLA, sold under the tradename VICRYL (Ethicon, Inc., Somerville, N.J.).
- VICRYL PGA/PLA
- One exemplary low density, open knitted mesh is Knitted VICRYL VKM-M, available from Ethicon, Inc., Somerville, NJ.
- the density or “openness” of a mesh material can be evaluated using a digital photocamera interfaced with a computer.
- the density of the mesh was determined using a Nikon SMZ-U Zoom with a Sony digital photocamera DKC-5000 interfaced with an IBM 300PL computer. Digital images of sections of each mesh magnified to 20' were manipulated using Image-Pro Plus 4.0 software in order to determine the mesh density. Once a digital image was captured by the software, the image was thresholded such that the area accounting for the empty spaces in the mesh could be subtracted from the total area of the image. The mesh density was taken to be the percentage of the remaining digital image. Implants with the most desirable mechanical properties were found to be those with a mesh density in the range of about 12 to 80% and more preferably about 45 to 80%.
- the biological component or effector of the issue repair stimulating implant can be incorporated within the implant before or after manufacture of the implant, or before or after the surgical placement of the implant.
- the implant comprising a foam and reinforcement layer can be placed in a suitable container comprising the biological component. After an appropriate time and under suitable conditions, the implant will become impregnated with the biological component.
- the biological component can be incorporated within the implant by, for example, using an appropriately gauged syringe to inject the effectors into the implant.
- Other methods well known to those of ordinary skill in the art can be applied in order to load an implant with an appropriate biological component, such as mixing, pressing, spreading, and placing the biological component into the implant.
- the biological component can be mixed with a gel-like carrier prior to injection into the implant.
- the gel-like carrier can be a biological or synthetic hydrogels, incluging alginates, cross-linked alginates, hyaluronic acid, collagen gel, poly(N-isopropylacrylamide), poly(oxyalkylene), copolymers of poly(ethylene oxide)-poly(propylene oxide), and blends thereof.
- an implant devoid of any biological component can be infused with effectors, or an implant with an existing biological component can be augmented with a supplemental quantity of the biological component.
- One method of incorporating a biological component within a surgically installed implant is by injection using an appropriately gauged syringe.
- the amount of the biological component included with an implant will vary depending on a variety of factors, including the size of the implant, the material from which the implant is made, the porosity of the implant, the identity of the biologically component, and the intended purpose of the implant.
- One of ordinary skill in the art can readily determine the appropriate quantity of biological component to include within an implant for a given application in order to facilitate and/or expedite the healing of tissue.
- the amount of biological component will, of course, vary depending upon the identity of the biological component and the given application.
- FIGS. 4 and 5 illustrate a mold set up useful with the present invention in which mold 18 has a base 21 and side walls 22 .
- Bottom shims 24 are disposed parallel to each other on an upper surface of base 21 .
- reinforcing fabric 25 is placed over the bottom shims 24 , and held in place by top shims 26 , that are disposed parallel to each other on the reinforcing fabric 25 .
- reinforcing fabric 25 can be placed between the bottom shims 24 and top shims 26 in a variety of ways. In one embodiment, the height of the bottom shims 24 can be varied so the mesh is placed nearer to the top or bottom surface of the sandwich construct.
- an electrostatically spun fabric barrier may be added to act as a barrier to hyperplasia and tissue adhesion, thus reducing the possibility of postsurgical adhesions.
- the fabric barrier is preferably in the form of dense fibrous fabric that is added to the implant.
- the fibrous fabric is comprised of small diameter fibers that are fused to the top and/or bottom surface of the foam component. This enables certain surface properties of the structure, such as porosity, permeability, degradation rate and mechanical properties, to be controlled.
- the fibrous fabric can be produced via an electrostatic spinning process in which a fibrous layer can be built up on a lyophilized foam surface.
- This electrostatic spinning process may be conducted using a variety of fiber materials.
- Exemplary fiber materials include aliphatic polyesters.
- a variety of solvents may be used as well, including those identified above that are useful to prepare the polymer solution that forms the foam component.
- the composition, thickness, and porosity of the fibrous layer may be controlled to provide the desired mechanical and biological characteristics.
- the bioabsorption rate of the fibrous layer may be selected to provide a longer or shorter bioabsorption profile as compared to the underlying foam layer.
- the fibrous layer may provide greater structural integrity to the composite so that mechanical force may be applied to the fibrous side of the structure.
- the fibrous layer could allow the use of sutures, staples or various fixation devices to hold the composite in place.
- the fibrous layer has a thickness in the range of about 1 micron to 1000 microns. However, for some applications such as rotator cuff and meniscus injury repair, the fibrous layer has a thickness greater than about 1.5 mm.
- the tissue repair stimulating implant is used in the treatment of a tissue injury, such as injury to a rotator cuff or meniscus.
- the implant can be of a size and shape such that it matches the geometry and dimensions of a desired portion or lesion of the tissue to be treated.
- the biological component may be added to the implant during or after manufacture of the implant or before or after the implant is installed in a patent. An additional quantity of the biological component may be added after the implant is installed.
- the implant Once access is made into the affected anatomical site (whether by minimally invasive or open surgical technique), the implant can be affixed to a desired position relative to the tissue injury, such as within a tear or lesion.
- the implant can be affixed by using a suitable technique.
- the implant can be affixed by a chemical and/or mechanical fastening technique.
- Suitable chemical fasteners include glues and/or adhesive such as fibrin glue, fibrin clot, and other known biologically compatible adhesives.
- Suitable mechanical fasteners include sutures, staples, tissue tacks, suture anchors, darts, screws, and arrows. It is understood that combinations of one or more chemical and/or mechanical fasteners can be used. Alternatively, one need not use any chemical and/or mechanical fasteners. Instead, placement of the implant can be accomplished through an interference fit of the implant with an appropriate site in the tissue to be treated.
- This example describes the preparation of three-dimensional elastomeric tissue implants with and without a reinforcement in the form of a biodegradable mesh.
- a solution of the polymer to be lyophilized to form the foam component was prepared in a four step process.
- a 95/5 weight ratio solution of 1,4-dioxane/(40/60 PCL/PLA) was made and poured into a flask.
- the flask was placed in a water bath, stirring at 70° C. for 5 hrs.
- the solution was filtered using an extraction thimble, extra coarse porosity, type ASTM 170-220 (EC) and stored in flasks.
- FIG. 6 is a scanning electron micrograph (SEM) of the knitted mesh. After preparing the meshes, 0.8-mm shims were placed at each end of a 15.3 ⁇ 15.3 cm aluminum mold, and the mesh was sized (14.2 mm) to fit the mold. The mesh was then laid into the mold, covering both shims.
- SEM scanning electron micrograph
- a clamping block was then placed on the top of the mesh and the shim such that the block was clamped properly to ensure that the mesh had a uniform height in the mold.
- Another clamping block was then placed at the other end, slightly stretching the mesh to keep it even and flat.
- the mold was tilted to about a 5 degree angle so that one of the non-clamping sides was higher than the other. Approximately 60 ml of the polymer solution was slowly transferred into the mold, ensuring that the solution was well dispersed in the mold. The mold was then placed on a shelf in a Virtis, Freeze Mobile G freeze dryer. The following freeze drying sequence was used: 1) 20° C. for 15 minutes; 2) ⁇ 5° C. for 120 minutes; 3) ⁇ 5° C. for 90 minutes under vacuum 100 milliTorr; 4) 5° C. for 90 minutes under vacuum 100 milliTorr; 5) 20° C. for 90 minutes under vacuum 100 milliTorr. The mold assembly was then removed from the freezer and placed in a nitrogen box overnight. Following the completion of this process the resulting implant was carefully peeled out of the mold in the form of a foam/mesh sheet.
- Nonreinforced foams were also fabricated. To obtain non-reinforced foams, however, the steps regarding the insertion of the mesh into the mold were not performed. The lyophilization steps above were followed.
- FIG. 7 is a scanning electron micrograph of a portion of an exemplary mesh-reinforced foam tissue implant formed by this process. The pores in this foam have been optimized for cell ingrowth.
- Example 1 Lyophilized 40/60 polycaprolactone/polylactic acid, (PCL/PLA) foam, as well as the same foam reinforced with an embedded VICRYL knitted mesh, were fabricated as described in Example 1. These reinforced implants were tested for suture pull-out strength and burst strength and compared to both standard VICRYL mesh and non-reinforced foam prepared following the procedure of Example 1.
- Specimens were tested both as fabricated, and after in vitro exposure. In vitro exposure was achieved by placing the implants in phosphate buffered saline (PBS) solutions held at 37° C. in a temperature controlled waterbath.
- PBS phosphate buffered saline
- the dimension of the specimens was approximately 5 cm ⁇ 9 cm. Specimens were tested for pull-out strength in the wale direction of the mesh (knitting machine axis).
- a size 0 polypropylene monofilament suture (Code 8834H), sold under the tradename PROLENE (by Ethicon, Inc., Somerville, N.J.) was passed through the mesh 6.25 mm from the edge of the specimens. The ends of the suture were clamped into the upper jaw and the mesh or the reinforced foam was clamped into the lower jaw of an Instron model 4501.
- the Instron machine with a 201b load cell, was activated using a cross-head speed of 2.54 cm per minute. The ends of the suture were pulled at a constant rate until failure occurred. The peak load (lbs) experienced during the pulling was recorded.
- the dimension of the specimens was approximately 15.25 cm ⁇ 15.25 cm.
- Specimens were tested on a Mullen tester (Model J, manufactured by B.F. Perkins, a Stendex company, a division of Roehlen Industries, Chicopee, Mass.). The test followed the standard operating procedure for a Mullen tester. Results are reported as pounds per square inch (psi) at failure.
- Lyophilized 40/60 polycaprolactone/polylactic acid (PCL/PLA) foam, as well as the same foam reinforced with an embedded VICRYL knitted mesh were fabricated as described in Example 1.
- the foam and mesh reinforced foam implant were packaged and sterilized with ethylene oxide gas following standard sterilization procedures.
- the animals used in this study were female Long-Evans rats supplied by Harlan Sprague Dawley, Inc. (Indianapolis, Ind.) and Charles River Laboratories (Portage, Mich.). The animals weighed between 200 and 350 g.
- the rats were individually weighed and anesthetized with an intraperitoneal injection of a mixture of ketamine hydrochloride (sold under the tradename KETASET, manufactured for Aveco Co., Inc., Fort Dodge, Iowa, by Fort Dodge Laboratories, Inc., Fort Dodge, Iowa,) (dose of 60 milligram/kg animal weight) and xylazine hydrochloride (sold under the tradename XYLAZINE, Fermenta Animal Health Co., Kansas City, Mo.) (dose of 10 milligrams/kg animal weight).
- KETASET manufactured for Aveco Co., Inc., Fort Dodge, Iowa, by Fort Dodge Laboratories, Inc., Fort Dodge, Iowa
- xylazine hydrochloride sold under the tradename XYLAZINE, Fermenta Animal Health Co., Kansas City, Mo.
- the entire abdomen from the forelimbs to the hindlimbs
- dorsum from the dorsal cervical area to the dorsal lumbosacral area
- the abdomen was then scrubbed with chlorhexidine diacetate, rinsed with alcohol, dried, and painted with an aqueous iodophor solution of 1% available iodine.
- the anesthetized and surgically prepared animal was transferred to the surgeon and placed in a supine position. Sterile drapes were applied to the prepared area using aseptic technique.
- a ventral midline skin incision (approximately 3-4 cm) was made to expose the abdominal muscles.
- a 2.5 cm incision was made in the abdominal wall, approximately 1 cm caudal to the xyphoid.
- the incision was sutured with size 3-0 VICRYL suture in a simple continuous pattern.
- One of the test articles, cut to approximately 5 cm in diameter, was placed over the sutured incision and 4 corner tacks were sutured (size 5-0 PROLENE) to the abdominal wall at approximately 11:00, 1:00, 5:00 and 7:00 o'clock positions.
- the skin incision was closed with skin staples or metal wound clips.
- the rat was returned to the prep area and the dorsum was scrubbed, rinsed with alcohol, and wiped with iodine as described previously for the abdomen.
- the rat was returned to a surgeon and placed in the desired recumbent position for dorsal implantation.
- a transverse skin incision approximately 2 cm in length, was made approximately 1 cm caudal to the caudal edge of the scapula.
- a pocket was made in the dorsal subcutis by separating the skin from the underlying connective tissue via transverse blunt dissection.
- the rats were sacrificed after two weeks or four weeks, and the dorsal subcutaneous implant was removed, trimmed, and fixed in 10% neutral buffered Formalin (20 ⁇ the tissue volume).
- the samples were processed in paraffin, cut into 5 mm sections, and stained with Hematoxylin Eosin (H & E).
- This example describes another embodiment of the present invention in which the preparation of a hybrid structure of a mesh reinforced foam is described.
- a knitted VICRYL mesh reinforced foam of 60/40 PLA/PCL was prepared as described in Example 1.
- the sheet was then covered with microfibrous bioabsorbable fabric produced by an electrostatic spinning process.
- the electrostatically spun fabric provides resistance to cell prevention from surrounding tissues and it enhances the sutureability of the implant.
- a custom made electrostatic spinning machine located at Ethicon Inc (Somerville, N.J.) was used for this experiment.
- a Spellman high voltage DC supply (Model No.: CZE30PN1000, Spellman High Voltage Electronics Corporation, Hauppauge, N.Y.) was used as high voltage source. Applied voltage as driving force and the speed of mandrel were controlled. Distance between the spinneret and the plate was mechanically controlled.
- Peel test specimens of mesh reinforced foam were made so as to separate otherwise bonded layers at one end to allow initial gripping required for a T-peel test (ref. ASTM D1876-95).
- PCL/PLA polycaprolactone/polylactic acid
- PGA/PLA polyglycolic/poly
- the knitted VICRYL mesh foamed specimens required less force (0.087+/ ⁇ 0.050 in*1 bf) to cause failure than did the woven VICRYL foamed specimens (0.269+/ ⁇ 0.054 in*1 bf). It is important to note that the mode of failure in the two constructs was different. In the woven mesh specimens, there was some evidence of peel, whereas in the knitted mesh specimens, there was none. In fact, in the knitted specimens there was no sign of crack propagation at the interface between layers. A rate dependency in peel for the woven mesh specimens was noted. The test rate of 0.25 cm/min was chosen due to the absence of peel and swift tear of the foam at higher separation rates.
- Test results reported herein consist of tests run at this cross-head speed for both types of mesh. A slower speed of 0.025 cm/min was tried for the knitted mesh construct to investigate the possible onset of peel at sufficiently low separation speeds. However, the slower speed did not result in any change in the mode of failure.
- Bovine chondrocytes were isolated from bovine shoulders as described by Buschmann, M.D. et al. (J.Orthop.Res.10, 745-752, 1992). Bovine chondrocytes were cultured in Dulbecco's modified eagles medium (DMEM-high glucose) supplemented with 10% fetal calf serum (FCS), 10 mM HEPES, 0.1 mM nonessential amino acids, 20 ⁇ g/ml L-proline, 50 ⁇ g/ml ascorbic acid, 100 U/ml penicillin, 100 ⁇ g/ml streptomycin and 0.25 ⁇ g/ml amphotericin B (growth media). Half of the medium was replenished every other day.
- DMEM-high glucose Dulbecco's modified eagles medium
- FCS fetal calf serum
- HEPES fetal calf serum
- nonessential amino acids 20 ⁇ g/ml L-proline
- the architecture of the scaffolds supported uniform cell seeding and matrix formation throughout the thickness of the scaffolds. Furthermore, the histological sections stained positively for Type II and GAG and weakly for collagen Type I indicating a cartilage-like matrix.
- a medial approach to the right stifle joint by osteotomy of the origin of the medial collateral ligament was taken to achieve full access to the medial meniscus. Approximately 60% of the central meniscus was excised in the red-white zone.
- the scaffold (+/ ⁇ reinforced mesh) was secured in the defect (9 ⁇ 5 ⁇ 2 mm) using 6 interrupted PROLENE sutures (6-0) on a C-1 taper needle (FIG. 9).
- the joint capsule, fascial, and skin layers were closed with PROLENE-0 or VICRYL 2-0 sutures.
- the goats were placed in a Schroeder-Thomas splint with an aluminum frame for 2 weeks to allow for partial weight bearing of the right stifle.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Medicinal Chemistry (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Materials Engineering (AREA)
- Engineering & Computer Science (AREA)
- Composite Materials (AREA)
- Dispersion Chemistry (AREA)
- Materials For Medical Uses (AREA)
- Prostheses (AREA)
Abstract
Description
- The present invention relates to bioabsorbable, porous, reinforced, biocompatible tissue repair stimulating implant devices comprising at least one biological component for use in the repair of orthopaedic type injuries, such as damage to the meniscus and rotator cuff, and methods for making such devices.
- Individuals can sometimes sustain an injury to tissue, such as cartilage, muscle, bone, and sinew that requires repair by surgical intervention. Such repairs can be effected by suturing or otherwise repairing the damaged tissue, and/or by augmenting the damaged tissue with other tissue or with a tissue implant. The implant can provide structural support to the damaged tissue.
- One example of a common tissue injury concerns damage to cartilage, for example, the menisci of a knee joint. There are two menisci of the knee joint, a medial and a lateral meniscus. The meniscus is a biconcave, fibrocartilage tissue that is interposed between the femur and tibia of the leg. The primary functions of the meniscus are to bear loads, absorb shock, stabilize, and lubricate the joint. If not treated properly, an injury to the meniscus, such as a “bucket-handle tear,” can lead to the development of osteoarthritis. Currently, treatment modalities for a damaged meniscus include removal of the meniscus and surgical repair of the damaged meniscus.
- Another common tissue injury is a damaged or torn rotator cuff, which facilitates circular motion of the humerus bone relative to the scapula. The most common injury associated with the rotator cuff is a strain or tear to the supraspinatus tendon. This tear can be at the insertion site of the tendon with the humerus, thereby releasing the tendon partially, or fully (depending upon the severity of the injury), from the bone. Additionally, the strain or tear can occur within the tendon itself. Treatment for a strained tendon usually involves physical cessation from use of the tendon. However, depending upon the severity of the injury, a torn tendon might require surgical intervention as in the case of a full tear of the supraspinatus tendon from the humerus. Surgical intervention can involve the repair and/or reattachment of torn tissue. A prolonged recovery period often follows repair of a rotator cuff tear.
- Surgical treatment of damaged tissue (e.g., the menisci or rotator cuff) would benefit from techniques that effect a more reliable repair of tissue, and which facilitate more rapid healing. Thus, various implants have been used in surgical procedures to help achieve these benefits. Examples of such implants include those that are made from biologically derived tissue (e.g., allografts and autografts), and those that are synthetic. Biologically derived materials can have disadvantages in that they can contribute to disease transmission, while synthetic materials are difficult to manufacture in such a way that their properties are reproducible from batch to batch.
- Various known devices and techniques for treating such conditions have been described in the prior art. For example, Naughton et al. (U.S. Pat. No. 5,842,477) describe an in vivo method of making and/or repairing cartilage by implanting a biocompatible structure in combination with periosteal/perichondrial tissue which facilitates the securing of the implant.
- Various tissue reinforcing materials are disclosed in U.S. Pat. No. 5,891,558 (Bell et al.) and European Patent Application No. 0 274 898 A2 (Hinsch). Bell et al. describe biopolymer foams and foam constructs that can be used in tissue repair and reconstruction. Hinsch describes an open cell, foam-like implant made from resorbable materials, which has one or more textile reinforcing elements embedded therein. Although potentially useful, the implant material is believed to lack sufficient strength and structural integrity to be effectively used as a tissue repair implant.
- Despite existing technology, there continues to be a need for devices and methods for securing damaged tissue and facilitating rapid healing of the damaged tissue.
- This invention relates to bioabsorbable, porous, reinforced, biocompatible tissue repair stimulating implant, or “scaffold,” devices for use in the repair and/or regeneration of diseased or damaged tissue, and the methods for making and using these devices. The implants comprise a bioabsorable polymeric foam component having pores with an open cell pore structure. The foam component is reinforced with a material such as a mesh. Preferably, the implant has sufficient structural integrity to enable it to be handled in the operating room prior to and during implantation. These implants should also have sufficient properties (e.g., tear strength) to enable them to accept and retain sutures or other fasteners without tearing. Desirable properties are imparted to the implant of the invention by integrating the foam component with the reinforcement component. That is, the pore-forming webs or walls of the foam component penetrate the mesh of the reinforcement component so as to interlock therewith. The implant may include one or more layers of each of the foam and reinforcement components. Preferably, adjacent layers of foam are also integrated by at least a partial interlocking of the pore-forming webs or walls in the adjacant layers. The implants of the instant invention further comprise at least one biological component that is incorporated therein.
- The reinforcement material is preferably a mesh, which may be bioabsorbable. The reinforcement should have a sufficient mesh density to permit suturing, but the density should not be so great as to impede proper bonding between the foam and the reinforcement. A preferred mesh density is in the range of about 12 to 80%.
- The biological component of the present invention comprises at least one effector molecule and/or cell, which contributes to the healing process of an injured tissue. Collectively, these materials are sometimes referred to herein as “effectors.” The effectors can be a cellular factor such as a protein or peptide (for the sake of simplicity, use of the term “protein” herein will include peptide), a non-protein biomolecule, a cell type, a pharmaceutical agent, or combinations thereof. One function of the implant of the current invention is as a carrier for the effectors, and the effector can be incorporated within the implant either prior to or following surgical placement of the implant.
- The invention also relates to a method of preparing such biocompatible, bioabsorbable tissue repair stimulating implants. The implants are made by placing a reinforcement material within a mold in a desired position and orientation. A solution of a desired polymeric material in a suitable solvent is added to the mold and the solution is lyophilized to obtain the implant in which a reinforcement material is embedded in a polymeric foam. The effector may be added to the implant, either during or after manufacture, by a variety of techniques.
- The tissue repair stimulating implant can be used to treat injuries ocurring within the musculoskeletal system, such as injuries to the rotator cuff or meniscus.
- The invention will be more fully understood by reference to the following detailed description when considered in conjunction with the accompanying drawings, in which:
- FIG. 1 is a sectional view of a tissue implant constructed according to the present invention;
- FIG. 2 is a sectional view of an alternative embodiment of the implant of the present invention;
- FIG. 3 is a sectional view of yet another embodiment of the implant of the present invention;
- FIG. 4 is a perspective view of one embodiment of a mold set-up useful with the present invention;
- FIG. 5 is a sectional view of a portion of the mold set-up of FIG. 4;
- FIG. 6 is a scanning electron micrograph of a bioabsorbable knitted mesh reinforcement material useful with the implant of the present invention; and
- FIG. 7 is a scanning electron micrograph of a portion of an implant according to the present invention.
- The present invention relates to a biocompatible tissue repair stimulating implant or “scaffold” device which, preferably, is bioabsorbable, and to methods for making and using such a device. The implant includes one or more layers of a bioabsorbable polymeric foam having pores with an open cell pore structure. A reinforcement component is also present within the implant to contribute enhanced mechanical and handling properties. The reinforcement component is preferably in the form of a mesh fabric that is biocompatible. The reinforcement component may be bioabsorbable as well. The implant has incorporated therein a biological component, or effector that assists in and/or expedites tissue healing. Preferably, the biological component is housed primarily within the pores of the foam component of the implant.
- In some surgical applications, such as for use in the repair of a torn rotator cuff or meniscus, the tissue implants of the invention must be able to be handled in the operating room, and they must be able to be sutured or otherwise fastened without tearing. Additionally, the implants should have a burst strength adequate to reinforce the tissue, and the structure of the implant must be suitable to encourage tissue ingrowth. A preferred tissue ingrowth-promoting structure is one where the cells of the foam component are open and sufficiently sized to permit cell ingrowth and to house the effector. A suitable pore size to accommodate these features is one in which the pores have an average diameter in the range of about 100 to 1000 microns and, more preferably, about 150 to 500 microns.
- Referring to FIGS. 1 through 3, the
implant 10 includes apolymeric foam component 12 and areinforcement component 14. The foam component preferably haspores 13 with an open cell pore structure. Although illustrated as having the reinforcement component disposed substantially in the center of a cross section of the implant, it is understood that the reinforcement material can be disposed at any location within the implant. Further, as shown in FIG. 2, more than one layer of each of the foam component 12 a, 12 b and reinforcement component 14 a, 14 b may be present in the implant. It is understood that various layers of the foam component and/or the reinforcement materials may be made from different materials and have different pore sizes. - FIG. 3 illustrates an embodiment in which a
barrier layer 16 is present in the implant. Although illustrated as being only on one surface of theimplant 10, thebarrier layer 16 may be present on either or both of the top andbottom surfaces - The
implant 10 must have sufficient structural integrity and physical properties to facilitate ease of handling in an operating room environment, and to permit it to accept and retain sutures or other fasteners without tearing. Adequate strength and physical properties are developed in the implant through the selection of materials used to form the foam and reinforcement components, and the manufacturing process. As shown in FIG. 7, thefoam component 12 is integrated with thereinforcement component 14 such that the web or walls of the foam componenets that form pores 13 penetrate the mesh of thereinforcement component 14 and interlock with the reinforcement component. The pore-forming walls in adjacent layers of the foam component also interlock with one another, regardless of whether the foam layers are separated by a layer of reinforcement materials or whether they are made of the same or different materials. - A variety of bioabsorbable polymers can be used to make porous, reinforced tissue repair stimulating implant or scaffold devices according to the present invention. Examples of suitable biocompatible, bioabsorbable polymers include polymers selected from the group consisting of aliphatic polyesters, poly(amino acids), copoly(ether-esters), polyalkylenes oxalates, polyamides, tyrosine derived polycarbonates, poly(iminocarbonates), polyorthoesters, polyoxaesters, polyamidoesters, polyoxaesters containing amine groups, poly(anhydrides), polyphosphazenes, biomolecules (i.e., biopolymers such as collagen, elastin, bioabsorbable starches, etc.) and blends thereof. For the purpose of this invention aliphatic polyesters include, but are not limited to, homopolymers and copolymers of lactide (which includes lactic acid, D-,L- and meso lactide), glycolide (including glycolic acid), ε-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3-dioxan-2-one), alkyl derivatives of trimethylene carbonate, δ-valerolactone, β-butyrolactone, γ-butyrolactone, ε-decalactone, hydroxybutyrate, hydroxyvalerate, 1 ,4-dioxepan-2-one (including its dimer 1,5,8,12-tetraoxacyclotetradecane-7,14-dione), 1,5-dioxepan-2-one, 6,6 -dimethyl-1,4-dioxan-2-
one 2,5-diketomorpholine, pivalolactone, α, α-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4-dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, 6,8-dioxabicycloctane-7-one and polymer blends thereof. Poly(iminocarbonates), for the purpose of this invention, are understood to include those polymers as described by Kemnitzer and Kohn, in the Handbook of Biodegradable Polymers, edited by Domb, et. al., Hardwood Academic Press, pp. 251-272 (1997). Copoly(ether-esters), for the purpose of this invention, are understood to include those copolyester-ethers as described in the Journal of Biomaterials Research, Vol. 22, pages 993-1009, 1988 by Cohn and Younes, and in Polymer Preprints (ACS Division of Polymer Chemistry), Vol. 30(1), page 498, 1989 by Cohn (e.g., PEO/PLA). Polyalkylene oxalates, for the purpose of this invention, include those described in U.S. Pat. Nos. 4,208,511; 4,141,087; 4,130,639; 4,140,678; 4,105,034; and 4,205,399. Polyphosphazenes, co-, ter- and higher order mixed monomer based polymers made from L-lactide, D,L-lactide, lactic acid, glycolide, glycolic acid, para-dioxanone, trimethylene carbonate and E-caprolactone such as are described by Allcock in The Encyclopedia of Polymer Science, Vol. 13, pages 31-41, Wiley Intersciences, John Wiley & Sons, 1988 and by Vandorpe, et al in the Handbook of Biodegradable Polymers, edited by Domb, et al., Hardwood Academic Press, pp. 161-182 (1997). Polyanhydrides include those derived from diacids of the form HOOC—C6H4—O-(CH 2)m—O—C6H4—COOH, where “m” is an integer in the range of from 2 to 8, and copolymers thereof with aliphatic alpha-omega diacids of up to 12 carbons. Polyoxaesters, polyoxaamides and polyoxaesters containing amines and/or amido groups are described in one or more of the following U.S. Pat. Nos. 5,464,929; 5,595,751; 5,597,579; 5,607,687; 5,618,552; 5,620,698; 5,645,850; 5,648,088; 5,698,213; 5,700,583; and 5,859,150. Polyorthoesters such as those described by Heller in Handbook of Biodegradable Polymers, edited by Domb, et al., Hardwood Academic Press, pp. 99-118 (1997). - As used herein, the term “glycolide” is understood to include polyglycolic acid. Further, the term “lactide” is understood to include L-lactide, D-lactide, blends thereof, and lactic acid polymers and copolymers.
- Currently, aliphatic polyesters are among the preferred absorbable polymers for use in making the foam implants according to the present invention. Aliphatic polyesters can be homopolymers, copolymers (random, block, segmented, tapered blocks, graft, triblock, etc.) having a linear, branched or star structure. Suitable monomers for making aliphatic homopolymers and copolymers may be selected from the group consisting of, but are not limited, to lactic acid, lactide (including L-, D-, meso and D,L mixtures), glycolic acid, glycolide, ε-caprolactone, p-dioxanone (1,4-dioxan-2-one), trimethylene carbonate (1,3 -dioxan-2-one), δ-valerolactone, β-butyrolactone, ε-decalactone, 2,5-diketomorpholine, pivalolactone, α, α-diethylpropiolactone, ethylene carbonate, ethylene oxalate, 3-methyl-1,4 -dioxane-2,5-dione, 3,3-diethyl-1,4-dioxan-2,5-dione, γ-butyrolactone, 1,4-dioxepan-2-one, 1,5-dioxepan-2-one, 6,6-dimethyl-dioxepan-2-one, 6,8-dioxabicycloctane-7-one, and combinations thereof.
- Elastomeric copolymers are also particularly useful in the present invention. Suitable elastomeric polymers include those with an inherent viscosity in the range of about 1.2 dL/g to 4 dL/g, more preferably about 1.2 dL/g to 2 dL/g and most preferably about 1.4 dL/g to 2 dL/g as determined at 25° C. in a 0.1 gram per deciliter (g/dL) solution of polymer in hexafluoroisopropanol (HFIP). Further, suitable elastomers exhibit a high percent elongation and a low modulus, while possessing good tensile strength and good recovery characteristics. In the preferred embodiments of this invention, the elastomer from which the foam component is formed exhibits a percent elongation (e.g., greater than about 200 percent and preferably greater than about 500 percent). In addition to these elongation and modulus properties, suitable elastomers should also have a tensile strength greater than about 500 psi, preferably greater than about 1,000 psi, and a tear strength of greater than about 50 lbs/inch, preferably greater than about 80 lbs/inch.
- Exemplary bioabsorbable, biocompatible elastomers include, but are not limited to, elastomeric copolymers of ε-caprolactone and glycolide (including polyglycolic acid) with a mole ratio of ε-caprolactone to glycolide of from about 35:65 to about 65:35, more preferably from 45:55 to 35:65; elastomeric copolymers of ε-caprolactone and lactide (including L-lactide, D-lactide, blends thereof, and lactic acid polymers and copolymers) where the mole ratio of ε-caprolactone to lactide is from about 35:65 to about 65:35 and more preferably from 45:55 to 30:70 or from about 95:5 to about 85:15; elastomeric copolymers of p-dioxanone (1,4-dioxan-2-one) and lactide (including L-lactide, D-lactide, blends thereof, and lactic acid polymers and copolymers) where the mole ratio of p-dioxanone to lactide is from about 40:60 to about 60:40; elastomeric copolymers of ε-caprolactone and p-dioxanone where the mole ratio of E-caprolactone to p-dioxanone is from about from 30:70 to about 70:30; elastomeric copolymers of p-dioxanone and trimethylene carbonate where the mole ratio of p-dioxanone to trimethylene carbonate is from about 30:70 to about 70:30; elastomeric copolymers of trimethylene carbonate and glycolide (including polyglycolic acid) where the mole ratio of trimethylene carbonate to glycolide is from about 30:70 to about 70:30; elastomeric copolymers of trimethylene carbonate and lactide (including L-lactide, D-lactide, blends thereof, and lactic acid polymers and copolymers) where the mole ratio of trimethylene carbonate to lactide is from about 30:70 to about 70:30; and blends thereof. Examples of suitable bioabsorbable elastomers are described in U.S. Pat. Nos. 4,045,418; 4,057,537 and 5,468,253.
- In one embodiment, the elastomer is a 35:65 copolymer of polyglycolic acid and polycaprolactone, formed in a dioxane solvent and including a polydioxanone mesh. In another embodiment, the elastomer is a 50:50 blend of a 35:65 copolymer of polyglycolic acid and polycaprolactone and 40:60 ε-caprolactone-co-lactide.
- One of ordinary skill in the art will appreciate that the selection of a suitable polymer or copolymer for forming the foam depends on several factors. The more relevant factors in the selection of the appropriate polymer(s) that is used to form the foam component include bioabsorption (or bio-degradation) kinetics; in vivo mechanical performance; cell response to the material in terms of cell attachment, proliferation, migration and differentiation; and biocompatibility. Other relevant factors, which to some extent dictate the in vitro and in vivo behavior of the polymer, include the chemical composition, spatial distribution of the constituents, the molecular weight of the polymer, and the degree of crystallinity.
- The ability of the material substrate to resorb in a timely fashion in the body environment is critical. But the differences in the absorption time under in vivo conditions can also be the basis for combining two different copolymers. For example, a copolymer of 35:65 ε-caprolactone and glycolide (a relatively fast absorbing polymer) is blended with 40:60 ε-caprolactone and L-lactide copolymer (a relatively slow absorbing polymer) to form a foam component. Depending upon the processing technique used, the two constituents can be either randomly inter-connected bicontinuous phases, or the constituents could have a gradient-like architecture in the form of a laminate type composite with a well integrated interface between the two constituent layers. The microstructure of these foams can be optimized to regenerate or repair the desired anatomical features of the tissue that is being engineered.
- In one embodiment, it is desirable to use polymer blends to form structures which transition from one composition to another composition in a gradient-like architecture. Foams having this gradient-like architecture are particularly advantageous in tissue engineering applications to repair or regenerate the structure of naturally occurring tissue such as cartilage (articular, meniscal, septal, tracheal, etc.), rotator cuff, esophagus, skin, bone, and vascular tissue. For example, by blending an elastomer of ε-caprolactone-co-glycolide with ε-caprolactone-co-lactide (e.g., with a mole ratio of about 5:95) a foam may be formed that transitions from a softer spongy material to a stiffer more rigid material in a manner similar to the transition from cartilage to bone. Clearly, one of ordinary skill in the art will appreciate that other polymer blends may be used for similar gradient effects, or to provide different gradients (e.g., different absorption profiles, stress response profiles, or different degrees of elasticity). For example, such design features can establish a concentration gradient for the biological component or effector such that a higher concentration of the effector is present in one region of the implant (e.g., an interior portion) than in another region (e.g., outer portions). This may be effected by engineering an implant in which the overall pore volume is greater in a region in which it is desired to have a greater concentration of biological component.
- The implants of the invention can also be used for organ repair replacement or regeneration strategies that may benefit from these unique tissue implants. For example, these implants can be used for spinal disc, cranial tissue, dura, nerve tissue, liver, pancreas, kidney, bladder, spleen, cardiac muscle, skeletal muscle, skin, fascia, maxillofacial, stomach, tendons, cartilage, ligaments, and breast tissues.
- The reinforcing component of the tissue repair stimulating implant of the present invention can be comprised of any absorbable or non-absorbable biocompatible material, including textiles with woven, knitted, warped knitted (i.e., lace-like), non-woven, and braided structures. In an exemplary embodiment, the reinforcing component has a mesh-like structure. In any of the above structures, mechanical properties of the material can be altered by changing the density or texture of the material, or by embedding particles in the material. The fibers used to make the reinforcing component can be monofilaments, yams, threads, braids, or bundles of fibers. These fibers can be made of any biocompatible material including bioabsorbable materials such as polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), polydioxanone (PDO), trimethylene carbonate (TMC), polyvinyl alcohol (PVA), copolymers or blends thereof. In one embodiment, the fibers are formed of a polylactic acid and polyglycolic acid copolymer at a 95:5 mole ratio.
- In another embodiment, the fibers that form the reinforcing material can be made of a bioabsorbable glass. Bioglass, a silicate containing calcium phosphate glass, or calcium phosphate glass with varying amounts of solid particles added to control resorption time are examples of materials that could be spun into glass fibers and used for the reinforcing material. Suitable solid particles that may be added include iron, magnesium, sodium, potassium, and combinations thereof.
- The reinforcing material may also be formed from a thin, perforation-containing elastomeric sheet with perforations to allow tissue ingrowth. Such a sheet could be made of blends or copolymers of polylactic acid (PLA), polyglycolic acid (PGA), polycaprolactone (PCL), and polydioxanone (PDO).
- In one embodiment, filaments that form the reinforcing material may be co-extruded to produce a filament with a sheath/core construction. Such filaments are comprised of a sheath of biodegradable polymer that surrounds one or more cores comprised of another biodegradable polymer. Filaments with a fast-absorbing sheath surrounding a slower-absorbing core may be desirable in instances where extended support is necessary for tissue ingrowth.
- One of ordinary skill in the art will appreciate that one or more layers of the reinforcing material may be used to reinforce the tissue implant of the invention. In addition, biodegradable reinforcing layers (e.g., meshes) of the same structure and chemistry or different structures and chemistries can be overlaid on top of one another to fabricate reinforced tissue implants with superior mechanical strength.
- The biological component that is incorporated within the implant can be selected from among a variety of effectors that, when present at the site of injury, promote healing and/or regeneration of the affected tissue. In addition to being compounds or agents that actually promote or expedite healing, the effectors may also include compounds or agents that prevent infection (e.g., antimicrobial agents and antibiotics), compounds or agents that reduce inflammation (e.g., anti-inflammatory agents), and compounds or agents that suppress the immune system (e.g., immunosuppressants). By way of example, other types of effectors present within the implant of the present invention include heterologous or autologous growth factors, proteins, glycoproteins, hormones, cytokines, glycosaminoglycans, nucleic acids, analgesics, and cell types. It is understood that one or more effectors of the same or different functionality may be incorporated within the implant.
- Examples of suitable effectors include the multitude of heterologous or autologous growth factors known to promote healing and/or regeneration of injured or damaged tissue. Exemplary growth factors include, but are not limited to, TGF-P, bone morphogenic protein, fibroblast growth factor, platelet-derived growth factor, vascular endothelial cell-derived growth factor (VEGF), epidermal growth factor, insulin-like growth factor, hepatocyte growth factor, and fragments thereof.
- The proteins that may be present within the implant include proteins that are secreted from a cell which is housed within the implant, as well as those that are present within the implant in an isolated form. The isolated form of a protein typically is one that is about 55% or greater in purity, i.e., isolated from other cellular proteins, molecules, debris, etc. More preferably, the isolated protein is one that is at least 65% pure, and most preferably one that is at least about 75 to 95% pure. Notwithstanding the above, one of ordinary skill in the art will appreciate that proteins having a purity below about 55% are still considered to be within the scope of this invention. As used herein, the term “protein” embraces glycoproteins, lipoproteins, proteoglycans, peptides, and fragments thereof. Examples of proteins useful as effectors include, but are not limited to, pleiotrophin, endothelin, tenascin, fibronectin, fibrinogen, vitronectin, V-CAM, I-CAM, N-CAM, selectin, cadherin, integrin, laminin, actin, myosin, collagen, microfilament, intermediate filament, antibody, elastin, fibrillin, and fragments thereof.
- Glycosaminoglycans, highly charged polysaccharides which play a role in cellular adhesion, may also serve as effectors according to the present invention. Exemplary glycosaminoglycans useful as effectors include, but are not limited to, heparan sulfate, heparin, chondroitin sulfate, dermatan sulfate, keratin sulfate, hyaluronan (also known as hyaluronic acid), and combinations thereof.
- Suitable cell types that can serve as effectors according to this invention include, but are not limited to, osteocytes, osteoblasts, osteoclasts, fibroblasts, stem cells, pluripotent cells, chondrocyte progenitors, chondrocytes, endothelial cells, macrophages, leukocytes, adipocytes, monocytes, plasma cells, mast cells, umbilical cord cells, stromal cells, mesenchymal stem cells, epithelial cells, myoblasts, and bone marrow cells. Cells typically have at their surface receptor molecules which are responsive to a cognate ligand (e.g., a stimulator). A stimulator is a ligand which when in contact with its cognate receptor induce the cell possessing the receptor to produce a specific biological action. For example, in response to a stimulator (or ligand) a cell may produce significant levels of secondary messengers, like Ca+2, which then will have subsequent effects upon cellular processes such as the phosphorylation of proteins, such as (keeping with our example) protein kinase C. In some instances, once a cell is stimulated with the proper stimulator, the cell secretes a cellular messenger usually in the form of a protein (including glycoproteins, proteoglycans, and lipoproteins). This cellular messenger can be an antibody (e.g., secreted from plasma cells), a hormone, (e.g., a paracrine, autocrine, or exocrine hormone), or a cytokine.
- The foam component of the tissue implant may be formed as a foam by a variety of techniques well known to those having ordinary skill in the art. For example, the polymeric starting materials may be foamed by lyophilization, supercritical solvent foaming (i.e., as described in EP 464,163), gas injection extrusion, gas injection molding or casting with an extractable material (e.g., salts, sugar or similar suitable materials).
- In one embodiment, the foam component of the engineered tissue repair stimulating implant devices of the present invention may be made by a polymer-solvent phase separation technique, such as lyophilization. Generally, however, a polymer solution can be separated into two phases by any one of the four techniques: (a) thermally induced gelation/crystallization; (b) non-solvent induced separation of solvent and polymer phases; (c) chemically induced phase separation, and (d) thermally induced spinodal decomposition. The polymer solution is separated in a controlled manner into either two distinct phases or two bicontinuous phases. Subsequent removal of the solvent phase usually leaves a porous structure of density less than the bulk polymer and pores in the micrometer ranges. See Microcellular Foams Via Phase Separation, J. Vac. Sci. Technolol., A. T. Young, Vol. 4(3), May/Jun 1986.
- The steps involved in the preparation of these foams include choosing the right solvents for the polymers to be lyophilized and preparing a homogeneous solution. Next, the polymer solution is subjected to a freezing and vacuum drying cycle. The freezing step phase separates the polymer solution and vacuum drying step removes the solvent by sublimation and/or drying, leaving a porous polymer structure or an interconnected open cell porous foam.
- Suitable solvents that may be used in the preparation of the foam component include, but are not limited to, formic acid, ethyl formate, acetic acid, hexafluoroisopropanol (HFIP), cyclic ethers (e.g., tetrahydrofuran (THF), dimethylene fluoride (DMF), and polydioxanone (PDO)), acetone, acetates of C2 to C5 alcohols (e.g., ethyl acetate and t-butylacetate), glyme (e.g., monoglyme, ethyl glyme, diglyme, ethyl diglyme, triglyme, butyl diglyme and tetraglyme), methylethyl ketone, dipropyleneglycol methyl ether, lactones (e.g., γ-valerolactone, δ-valerolactone, β-butyrolactone, γ-butyrolactone), 1,4-dioxane, 1,3-dioxolane, 1,3-dioxolane-2-one (ethylene carbonate), dimethlycarbonate, benzene, toluene, benzyl alcohol, p-xylene, naphthalene, tetrahydrofuran, N-methyl pyrrolidone, dimethylformamide, chloroform, 1,2-dichloromethane, morpholine, dimethylsulfoxide, hexafluoroacetone sesquihydrate (HFAS), anisole and mixtures thereof. Among these solvents, a preferred solvent is 1,4-dioxane. A homogeneous solution of the polymer in the solvent is prepared using standard techniques.
- The applicable polymer concentration or amount of solvent that may be utilized will vary with each system. Generally, the amount of polymer in the solution can vary from about 0.5% to about 90% and, preferably, will vary from about 0.5% to about 30% by weight, depending on factors such as the solubility of the polymer in a given solvent and the final properties desired in the foam.
- In one embodiment, solids may be added to the polymer-solvent system to modify the composition of the resulting foam surfaces. As the added particles settle out of solution to the bottom surface, regions will be created that will have the composition of the added solids, not the foamed polymeric material. Alternatively, the added solids may be more concentrated in desired regions (i.e., near the top, sides, or bottom) of the resulting tissue implant, thus causing compositional changes in all such regions. For example, concentration of solids in selected locations can be accomplished by adding metallic solids to a solution placed in a mold made of a magnetic material (or vice versa).
- A variety of types of solids can be added to the polymer-solvent system. Preferably, the solids are of a type that will not react with the polymer or the solvent. Generally, the added solids have an average diameter of less than about 1.0 mm and preferably will have an average diameter of about 50 to about 500 microns. Preferably, the solids are present in an amount such that they will constitute from about 1 to about 50 volume percent of the total volume of the particle and polymer-solvent mixture (wherein the total volume percent equals 100 volume percent).
- Exemplary solids include, but are not limited to, particles of demineralized bone, calcium phosphate particles, Bioglass particles, calcium sulfate, or calcium carbonate particles for bone repair, leachable solids for pore creation and particles of bioabsorbable polymers not soluble in the solvent system that are effective as reinforcing materials or to create pores as they are absorbed, and non-bioabsorbable materials.
- Suitable leachable solids include nontoxic leachable materials such as salts (e.g., sodium chloride, potassium chloride, calcium chloride, sodium tartrate, sodium citrate, and the like), biocompatible mono and disaccharides (e.g., glucose, fructose, dextrose, maltose, lactose and sucrose), polysaccharides (e.g., starch, alginate, chitosan), water soluble proteins (e.g., gelatin and agarose). The leachable materials can be removed by immersing the foam with the leachable material in a solvent in which the particle is soluble for a sufficient amount of time to allow leaching of substantially all of the particles, but which does not dissolve or detrimentally alter the foam. The preferred extraction solvent is water, most preferably distilled-deionized water. Such a process is described in U.S. Pat. No. 5,514,378.
- Preferably the foam will be dried after the leaching process is complete at low temperature and/or vacuum to minimize hydrolysis of the foam unless accelerated absorption of the foam is desired.
- Suitable non-bioabsorbable materials include biocompatible metals such as stainless steel, cobalt chrome, titanium and titanium alloys, and bioinert ceramic particles (e.g., alumina, zirconia, and calcium sulfate particles). Further, the non-bioabsorbable materials may include polymers such as polyethylene, polyvinylacetate, polymethylmethacrylate, silicone, polyethylene oxide, polyethylene glycol, polyurethanes, polyvinyl alcohol, natural biopolymers (e.g., cellulose particles, chitin, keratin, silk, and collagen particles), and fluorinated polymers and copolymers (e.g., polyvinylidene fluoride, polytetrafluoroethylene, and hexafluoropropylene).
- It is also possible to add solids (e.g., barium sulfate) that will render the tissue implants radio opaque. The solids that may be added also include those that will promote tissue regeneration or regrowth, as well as those that act as buffers, reinforcing materials or porosity modifiers.
- As noted above, porous, reinforced tissue repair stimulating implant devices of the present invention are made by injecting, pouring, or otherwise placing, the appropriate polymer solution into a mold set-up comprised of a mold and the reinforcing elements of the present invention. The mold set-up is cooled in an appropriate bath or on a refrigerated shelf and then lyophilized, thereby providing a reinforced tissue engineered scaffold. The biological component can be added either before or after the lyophilization step. In the course of forming the foam component, it is believed to be important to control the rate of freezing of the polymer-solvent system. The type of pore morphology that is developed during the freezing step is a function of factors such as the solution thermodynamics, freezing rate, temperature to which it is cooled, concentration of the solution, and whether homogeneous or heterogenous nucleation occurs. One of ordinary skill in the art can readily optimize the parameters without undue experimentation.
- The required general processing steps include the selection of the appropriate materials from which the polymeric foam and the reinforcing components are made. If a mesh reinforcing material is used, the proper mesh density must be selected. Further, the reinforcing material must be properly aligned in the mold, the polymer solution must be added at an appropriate rate and, preferably, into a mold that is tilted at an appropriate angle to avoid the formation of air bubbles, and the polymer solution must be lyophilized.
- In embodiments that utilize a mesh reinforcing material, the reinforcing mesh has to be of a certain density. That is, the openings in the mesh material must be sufficiently small to render the construct sutureable or otherwise fastenable, but not so small as to impede proper bonding between the foam and the reinforcing mesh as the foam material and the open cells and cell walls thereof penetrate the mesh openings. Without proper bonding the integrity of the layered structure is compromised leaving the construct fragile and difficult to handle.
- During the lyophilization of the reinforced foam, several parameters and procedures are important to produce implants with the desired integrity and mechanical properties. Preferably, the reinforcement material is substantially flat when placed in the mold. To ensure the proper degree of flatness, the reinforcement (e.g., mesh) is pressed flat using a heated press prior to its placement within the mold. Further, in the event that reinforcing structures are not isotropic it is desirable to indicate this anisotropy by marking the construct to indicate directionality. This can be accomplished by embedding one or more indicators, such as dyed markings or dyed threads, within the woven reinforcements. The direction or orientation of the indicator will indicate to a surgeon the dimension of the implant in which physical properties are superior.
- As noted above, the manner in which the polymer solution is added to the mold prior to lyophilization helps contribute to the creation of a tissue implant with adequate mechanical integrity. Assuming that a mesh reinforcing material will be used, and that it will be positioned between two thin (e.g., 0.75 mm), shims it should be positioned in a substantially flat orientation at a desired depth in the mold. The polymer solution is poured in a way that allows air bubbles to escape from between the layers of the foam component. Preferably, the mold is tilted at a desired angle and pouring is effected at a controlled rate to best prevent bubble formation. One of ordinary skill in the art will appreciate that a number of variables will control the tilt angle and pour rate. Generally, the mold should be tilted at an angle of greater than about 1 degree to avoid bubble formation. In addition, the rate of pouring should be slow enough to enable any air bubbles to escape from the mold, rather than to be trapped in the mold.
- If a mesh material is used as the reinforcing component, the density of the mesh openings is an important factor in the formation of a resulting tissue implant with the desired mechanical properties. A low density, or open knitted mesh material, is preferred. One particularly preferred material is a 90/10 copolymer of PGA/PLA, sold under the tradename VICRYL (Ethicon, Inc., Somerville, N.J.). One exemplary low density, open knitted mesh is Knitted VICRYL VKM-M, available from Ethicon, Inc., Somerville, NJ.
- The density or “openness” of a mesh material can be evaluated using a digital photocamera interfaced with a computer. In one evaluation, the density of the mesh was determined using a Nikon SMZ-U Zoom with a Sony digital photocamera DKC-5000 interfaced with an IBM 300PL computer. Digital images of sections of each mesh magnified to 20' were manipulated using Image-Pro Plus 4.0 software in order to determine the mesh density. Once a digital image was captured by the software, the image was thresholded such that the area accounting for the empty spaces in the mesh could be subtracted from the total area of the image. The mesh density was taken to be the percentage of the remaining digital image. Implants with the most desirable mechanical properties were found to be those with a mesh density in the range of about 12 to 80% and more preferably about 45 to 80%.
- The biological component or effector of the issue repair stimulating implant can be incorporated within the implant before or after manufacture of the implant, or before or after the surgical placement of the implant.
- Prior to surgical placement, the implant comprising a foam and reinforcement layer can be placed in a suitable container comprising the biological component. After an appropriate time and under suitable conditions, the implant will become impregnated with the biological component. Alternatively, the biological component can be incorporated within the implant by, for example, using an appropriately gauged syringe to inject the effectors into the implant. Other methods well known to those of ordinary skill in the art can be applied in order to load an implant with an appropriate biological component, such as mixing, pressing, spreading, and placing the biological component into the implant. Alternatively, the biological component can be mixed with a gel-like carrier prior to injection into the implant. The gel-like carrier can be a biological or synthetic hydrogels, incluging alginates, cross-linked alginates, hyaluronic acid, collagen gel, poly(N-isopropylacrylamide), poly(oxyalkylene), copolymers of poly(ethylene oxide)-poly(propylene oxide), and blends thereof.
- Following surgical placement, an implant devoid of any biological component can be infused with effectors, or an implant with an existing biological component can be augmented with a supplemental quantity of the biological component. One method of incorporating a biological component within a surgically installed implant is by injection using an appropriately gauged syringe.
- The amount of the biological component included with an implant will vary depending on a variety of factors, including the size of the implant, the material from which the implant is made, the porosity of the implant, the identity of the biologically component, and the intended purpose of the implant. One of ordinary skill in the art can readily determine the appropriate quantity of biological component to include within an implant for a given application in order to facilitate and/or expedite the healing of tissue. The amount of biological component will, of course, vary depending upon the identity of the biological component and the given application.
- FIGS. 4 and 5 illustrate a mold set up useful with the present invention in which
mold 18 has abase 21 andside walls 22. Bottom shims 24 are disposed parallel to each other on an upper surface ofbase 21. Although parallel alignment of bottom shims 24 is illustrated, any number of shims, as well as any desired alignment, may be utilized. As further illustrated, reinforcingfabric 25 is placed over the bottom shims 24, and held in place bytop shims 26, that are disposed parallel to each other on the reinforcingfabric 25. Though not shown, reinforcingfabric 25 can be placed between thebottom shims 24 andtop shims 26 in a variety of ways. In one embodiment, the height of the bottom shims 24 can be varied so the mesh is placed nearer to the top or bottom surface of the sandwich construct. - In another embodiment, an electrostatically spun fabric barrier may be added to act as a barrier to hyperplasia and tissue adhesion, thus reducing the possibility of postsurgical adhesions. The fabric barrier is preferably in the form of dense fibrous fabric that is added to the implant. Preferably, the fibrous fabric is comprised of small diameter fibers that are fused to the top and/or bottom surface of the foam component. This enables certain surface properties of the structure, such as porosity, permeability, degradation rate and mechanical properties, to be controlled.
- One of ordinary skill in the art will appreciate that the fibrous fabric can be produced via an electrostatic spinning process in which a fibrous layer can be built up on a lyophilized foam surface. This electrostatic spinning process may be conducted using a variety of fiber materials. Exemplary fiber materials include aliphatic polyesters. A variety of solvents may be used as well, including those identified above that are useful to prepare the polymer solution that forms the foam component.
- The composition, thickness, and porosity of the fibrous layer may be controlled to provide the desired mechanical and biological characteristics. For example, the bioabsorption rate of the fibrous layer may be selected to provide a longer or shorter bioabsorption profile as compared to the underlying foam layer. Additionally, the fibrous layer may provide greater structural integrity to the composite so that mechanical force may be applied to the fibrous side of the structure. In one embodiment the fibrous layer could allow the use of sutures, staples or various fixation devices to hold the composite in place. Generally, the fibrous layer has a thickness in the range of about 1 micron to 1000 microns. However, for some applications such as rotator cuff and meniscus injury repair, the fibrous layer has a thickness greater than about 1.5 mm.
- In one embodiment of the present invention, the tissue repair stimulating implant is used in the treatment of a tissue injury, such as injury to a rotator cuff or meniscus. The implant can be of a size and shape such that it matches the geometry and dimensions of a desired portion or lesion of the tissue to be treated. As noted above, the biological component may be added to the implant during or after manufacture of the implant or before or after the implant is installed in a patent. An additional quantity of the biological component may be added after the implant is installed. Once access is made into the affected anatomical site (whether by minimally invasive or open surgical technique), the implant can be affixed to a desired position relative to the tissue injury, such as within a tear or lesion. Once the implant is placed in the desired position or lesion, it can be affixed by using a suitable technique. In one aspect, the implant can be affixed by a chemical and/or mechanical fastening technique. Suitable chemical fasteners include glues and/or adhesive such as fibrin glue, fibrin clot, and other known biologically compatible adhesives. Suitable mechanical fasteners include sutures, staples, tissue tacks, suture anchors, darts, screws, and arrows. It is understood that combinations of one or more chemical and/or mechanical fasteners can be used. Alternatively, one need not use any chemical and/or mechanical fasteners. Instead, placement of the implant can be accomplished through an interference fit of the implant with an appropriate site in the tissue to be treated.
- One of ordinary skill in the art will appreciate that the identity of the effector(s) that serve as the biological component may be determined by a surgeon, based on principles of medical science and the applicable treatment objectives.
- The following examples are illustrative of the principles and practice of this invention. Numerous additional embodiments within the scope and spirit of the invention will become apparent to those skilled in the art.
- This example describes the preparation of three-dimensional elastomeric tissue implants with and without a reinforcement in the form of a biodegradable mesh.
- A solution of the polymer to be lyophilized to form the foam component was prepared in a four step process. A 95/5 weight ratio solution of 1,4-dioxane/(40/60 PCL/PLA) was made and poured into a flask. The flask was placed in a water bath, stirring at 70° C. for 5 hrs. The solution was filtered using an extraction thimble, extra coarse porosity, type ASTM 170-220 (EC) and stored in flasks.
- Reinforcing mesh materials formed of a 90/10 copolymer of polyglycolic/polylactic acid (PGA/PLA) knitted (Code VKM-M) and woven (Code VWM-M), both sold under the tradename VICRYL were rendered flat by ironing, using a compression molder at 80° C./2 min. FIG. 6 is a scanning electron micrograph (SEM) of the knitted mesh. After preparing the meshes, 0.8-mm shims were placed at each end of a 15.3×15.3 cm aluminum mold, and the mesh was sized (14.2 mm) to fit the mold. The mesh was then laid into the mold, covering both shims. A clamping block was then placed on the top of the mesh and the shim such that the block was clamped properly to ensure that the mesh had a uniform height in the mold. Another clamping block was then placed at the other end, slightly stretching the mesh to keep it even and flat.
- As the polymer solution was added to the mold, the mold was tilted to about a 5 degree angle so that one of the non-clamping sides was higher than the other. Approximately 60 ml of the polymer solution was slowly transferred into the mold, ensuring that the solution was well dispersed in the mold. The mold was then placed on a shelf in a Virtis, Freeze Mobile G freeze dryer. The following freeze drying sequence was used: 1) 20° C. for 15 minutes; 2)−5° C. for 120 minutes; 3)−5° C. for 90 minutes under vacuum 100 milliTorr; 4) 5° C. for 90 minutes under vacuum 100 milliTorr; 5) 20° C. for 90 minutes under vacuum 100 milliTorr. The mold assembly was then removed from the freezer and placed in a nitrogen box overnight. Following the completion of this process the resulting implant was carefully peeled out of the mold in the form of a foam/mesh sheet.
- Nonreinforced foams were also fabricated. To obtain non-reinforced foams, however, the steps regarding the insertion of the mesh into the mold were not performed. The lyophilization steps above were followed.
- FIG. 7 is a scanning electron micrograph of a portion of an exemplary mesh-reinforced foam tissue implant formed by this process. The pores in this foam have been optimized for cell ingrowth.
- Lyophilized 40/60 polycaprolactone/polylactic acid, (PCL/PLA) foam, as well as the same foam reinforced with an embedded VICRYL knitted mesh, were fabricated as described in Example 1. These reinforced implants were tested for suture pull-out strength and burst strength and compared to both standard VICRYL mesh and non-reinforced foam prepared following the procedure of Example 1.
- Specimens were tested both as fabricated, and after in vitro exposure. In vitro exposure was achieved by placing the implants in phosphate buffered saline (PBS) solutions held at 37° C. in a temperature controlled waterbath.
- For the suture pull-out strength test, the dimension of the specimens was approximately 5 cm×9 cm. Specimens were tested for pull-out strength in the wale direction of the mesh (knitting machine axis). A size0 polypropylene monofilament suture (Code 8834H), sold under the tradename PROLENE (by Ethicon, Inc., Somerville, N.J.) was passed through the mesh 6.25 mm from the edge of the specimens. The ends of the suture were clamped into the upper jaw and the mesh or the reinforced foam was clamped into the lower jaw of an Instron model 4501. The Instron machine, with a 201b load cell, was activated using a cross-head speed of 2.54 cm per minute. The ends of the suture were pulled at a constant rate until failure occurred. The peak load (lbs) experienced during the pulling was recorded.
- The results of this test are shown below in Table 1.
TABLE 1 Suture Pull-Out Data (lbs) Time Foam Mesh Foamed Mesh 0 Day 0.46 5.3 +/− 0.8 5.7 +/− 0.3 7 Day — 4.0 +/− 1.0 5.0 +/− 0.5 - For the burst strength test, the dimension of the specimens was approximately 15.25 cm×15.25 cm. Specimens were tested on a Mullen tester (Model J, manufactured by B.F. Perkins, a Stendex company, a division of Roehlen Industries, Chicopee, Mass.). The test followed the standard operating procedure for a Mullen tester. Results are reported as pounds per square inch (psi) at failure.
- The results of the burst strength test are shown in Table 2.
TABLE 2 Burst Strength Data (psi) Time Point-Knitted VICRYL Mesh Foamed Knitted Mesh 0 Day 1349.5 1366.8 7 Day 1109.4 1279.6 - Mesh reinforced foam implants were implanted in an animal study and compared to currently used pelvic floor repair materials. The purpose of this animal study was to evaluate the subcutaneous tissue reaction and absorption of various polymer scaffolds. The tissue reaction and absorption was assessed grossly and histologically at 14 and 28 days post-implantation in the dorsal subcutis. In addition, the effect of these scaffolds on the bursting strength of incisional wounds in the abdominal musculature was determined. Burst testing was done at 14 and 28 days on ventrally placed implants and the attached layer of abdominal muscle.
- Lyophilized 40/60 polycaprolactone/polylactic acid (PCL/PLA) foam, as well as the same foam reinforced with an embedded VICRYL knitted mesh were fabricated as described in Example 1. The foam and mesh reinforced foam implant were packaged and sterilized with ethylene oxide gas following standard sterilization procedures. Controls for the study included: a VICRYL mesh control, a mechanical control (No mesh placed), and a processed porcine corium, sold under the tradename DermMatrix (by Advanced UroScience, St. Paul, Minn.) control.
- The animals used in this study were female Long-Evans rats supplied by Harlan Sprague Dawley, Inc. (Indianapolis, Ind.) and Charles River Laboratories (Portage, Mich.). The animals weighed between 200 and 350 g. The rats were individually weighed and anesthetized with an intraperitoneal injection of a mixture of ketamine hydrochloride (sold under the tradename KETASET, manufactured for Aveco Co., Inc., Fort Dodge, Iowa, by Fort Dodge Laboratories, Inc., Fort Dodge, Iowa,) (dose of 60 milligram/kg animal weight) and xylazine hydrochloride (sold under the tradename XYLAZINE, Fermenta Animal Health Co., Kansas City, Mo.) (dose of 10 milligrams/kg animal weight). After induction of anesthesia, the entire abdomen (from the forelimbs to the hindlimbs) and dorsum (from the dorsal cervical area to the dorsal lumbosacral area) was clipped free of hair using electric animal clippers. The abdomen was then scrubbed with chlorhexidine diacetate, rinsed with alcohol, dried, and painted with an aqueous iodophor solution of 1% available iodine. The anesthetized and surgically prepared animal was transferred to the surgeon and placed in a supine position. Sterile drapes were applied to the prepared area using aseptic technique.
- A ventral midline skin incision (approximately 3-4 cm) was made to expose the abdominal muscles. A 2.5 cm incision was made in the abdominal wall, approximately 1 cm caudal to the xyphoid. The incision was sutured with size 3-0 VICRYL suture in a simple continuous pattern. One of the test articles, cut to approximately 5 cm in diameter, was placed over the sutured incision and 4 corner tacks were sutured (size 5-0 PROLENE) to the abdominal wall at approximately 11:00, 1:00, 5:00 and 7:00 o'clock positions. The skin incision was closed with skin staples or metal wound clips.
- After the surgeon completed the laparotomy closure, mesh implant, and abdominal skin closure, the rat was returned to the prep area and the dorsum was scrubbed, rinsed with alcohol, and wiped with iodine as described previously for the abdomen. Once the dorsum was prepped, the rat was returned to a surgeon and placed in the desired recumbent position for dorsal implantation. A transverse skin incision, approximately 2 cm in length, was made approximately 1 cm caudal to the caudal edge of the scapula. A pocket was made in the dorsal subcutis by separating the skin from the underlying connective tissue via transverse blunt dissection. One of the test materials cut to approximately 2.0×2.0 cm square, was then inserted into the pocket and the skin incision closed with skin staples or metal wound clips.
- Each animal was observed daily after surgery to determine its health status on the basis of general attitude and appearance, food consumption, fecal and urinary excretion and presence of abnormal discharges.
- The animals utilized in this study were handled and maintained in accordance with current requirements of the Animal Welfare Act. Compliance with the above Public Laws was accomplished by adhering to the Animal Welfare regulations (9 CFR) and conforming to the current standards promulgated in the Guide for the Care and Use of Laboratory Animals.
- For the histopathology study, the rats were sacrificed after two weeks or four weeks, and the dorsal subcutaneous implant was removed, trimmed, and fixed in 10% neutral buffered Formalin (20× the tissue volume). The samples were processed in paraffin, cut into 5 mm sections, and stained with Hematoxylin Eosin (H & E).
- Dorsal samples for tissue reaction assessment were cut to approximate 2.0 cm squares. Ventral samples for burst testing were cut to approximate 5.0 cm diameter circles.
- The bursting strength of each specimen was measured together with the attached underlying abdominal muscle layer following the method of Example 2. The results of the burst strength tests are shown in Table 3.
TABLE 3 Burst Strength (psi) Sample 14 Days 28 Days Mesh Reinforced Foam 81.8 +/− 17.3 73 +/− 4.5 Dermatrix 70 +/− 4.0 70* - The histopathology study showed the mesh reinforced foam constructs had the highest degree of fibrous ingrowth and most robust encapsulation of all the implants tested at both time points. This fibrous reaction was mild in extent at 28 days.
- This example describes another embodiment of the present invention in which the preparation of a hybrid structure of a mesh reinforced foam is described.
- A knitted VICRYL mesh reinforced foam of 60/40 PLA/PCL was prepared as described in Example 1. A sheet, 2.54 cm×6.35 cm, was attached on a metal plate connected with a ground wire. The sheet was then covered with microfibrous bioabsorbable fabric produced by an electrostatic spinning process. The electrostatically spun fabric provides resistance to cell prevention from surrounding tissues and it enhances the sutureability of the implant.
- A custom made electrostatic spinning machine located at Ethicon Inc (Somerville, N.J.) was used for this experiment. A Spellman high voltage DC supply (Model No.: CZE30PN1000, Spellman High Voltage Electronics Corporation, Hauppauge, N.Y.) was used as high voltage source. Applied voltage as driving force and the speed of mandrel were controlled. Distance between the spinneret and the plate was mechanically controlled.
- A 14% solution of a 60/40 PLA/PCL copolymer produced at Corporate Biomaterials Center, a Division of Ethicon. Inc, Somerville, N.J. was prepared in trichloroethane chloride (TEC) solvent. The polymer solution was placed into a spinneret and high voltage was applied to the polymer solution. This experiment was performed at ambient temperature and humidity. The operating conditions during spinning were as follows:
Spinneret voltage: 25,000 V Plate voltage: Grounded Spinneret to mandrel distance: 15 cm - This process resulted in a deposited porous elastomeric polymer of approximately 10-500 μm in thickness on the surface of the mesh reinforced foam.
- Peel test specimens of mesh reinforced foam were made so as to separate otherwise bonded layers at one end to allow initial gripping required for a T-peel test (ref. ASTM D1876-95).
- Copolymer foams of 40/60 polycaprolactone/polylactic acid (PCL/PLA), reinforced with both 90/10 copolymer of polyglycolic/polylactic acid (PGA/PLA) knitted (Code VKM-M) and woven (Code VWM-M) meshes, were fabricated as described in Example 1. Test specimens strips, 2.0 cm×11.0 cm, were cut from the reinforced foam. Due to the cost of labor and materials, the size of the specimens was less than that cited in the above ASTM standard. The non-bonded section for gripping was produced by applying an aluminum foil blocker at one end to inhibit the penetration of polymer solution through the mesh reinforcement. The specimens were tested in an Instron Model 4501 Electromechanical Screw Test Machine. The initial distance between grips was 2.0 cm. The cross-head speed for all tests was held constant at 0.25 cm/min. The number of specimens of each construct tested was five.
- The knitted VICRYL mesh foamed specimens required less force (0.087+/−0.050 in*1 bf) to cause failure than did the woven VICRYL foamed specimens (0.269+/−0.054 in*1 bf). It is important to note that the mode of failure in the two constructs was different. In the woven mesh specimens, there was some evidence of peel, whereas in the knitted mesh specimens, there was none. In fact, in the knitted specimens there was no sign of crack propagation at the interface between layers. A rate dependency in peel for the woven mesh specimens was noted. The test rate of 0.25 cm/min was chosen due to the absence of peel and swift tear of the foam at higher separation rates. Test results reported herein consist of tests run at this cross-head speed for both types of mesh. A slower speed of 0.025 cm/min was tried for the knitted mesh construct to investigate the possible onset of peel at sufficiently low separation speeds. However, the slower speed did not result in any change in the mode of failure.
- In conclusion, the higher density of the woven mesh inhibited extensive penetration of polymeric foam and resulted in the dissipation of energy through the peeling of the foam from the mesh when subjected to a T-peel test at a cross-head speed of 0.25 cm/min. In the case of the lower density knitted mesh construct, there appeared to be little to no separation of foam from the mesh. In these experiments it appeared that the load was wholly dissipated by the cohesive tearing of the foam.
- Primary chondrocytes were isolated from bovine shoulders as described by Buschmann, M.D. et al. (J.Orthop.Res.10, 745-752, 1992). Bovine chondrocytes were cultured in Dulbecco's modified eagles medium (DMEM-high glucose) supplemented with 10% fetal calf serum (FCS), 10 mM HEPES, 0.1 mM nonessential amino acids, 20 μg/ml L-proline, 50 μg/ml ascorbic acid, 100 U/ml penicillin, 100 μg/ml streptomycin and 0.25 μg/ml amphotericin B (growth media). Half of the medium was replenished every other day.
- 5 mm×2 mm discs or scaffolds were cut from reinforced foam polymer sheets (60/40 PLA/PCL foam reinforced with 90/10 PGA/PLA) prepared as described in Example 1. These discs were sterilized for 20 minutes in 70% ethanol followed by five rinses of phosphate-buffered saline (PBS).
- Freshly isolated bovine chondrocytes were seeded at 5×106 cells (in 50 μl medium) by a static seeding method in hydrogel-coated plates (ultra low cluster dishes, Costar). Following 6 hours of incubation in a humidified incubator, the scaffolds were replenished with 2 ml of growth media. The scaffolds were cultured statically for up to 6 weeks in growth media.
- Constructs harvested at various time points (3 and 6 weeks) were fixed in 10% buffered formalin, embedded in paraffin and sectioned. Sections were stained with Safranin-O (SO; sulfated glycosaminoglycans—GAG's) or immunostained for collagen type I and II. Three samples per time point were sectioned and stained.
- Following 3-6 weeks of culturing under static conditions, the architecture of the scaffolds supported uniform cell seeding and matrix formation throughout the thickness of the scaffolds. Furthermore, the histological sections stained positively for Type II and GAG and weakly for collagen Type I indicating a cartilage-like matrix.
- Lyophilized 60/40 PLA/PCL foam, as well as the same foam reinforced with an embedded Vicryl (90/10 PGA/PLA) knitted mesh were fabricated analogous to the method described in Example 1, packaged and sterilized with ethylene oxide gas.
- Animals were housed and cared for at Ethicon, Inc. (Somerville, N.J.) under an approved institutional protocol. Three neutered male adult Neubian goats (50-65 Kg) were used in the study. An analgesic, Buprenorphine hydrochloride, was administered subcutaneously (0.005 mg/kg) about 2-3 hrs before the start of the surgery. Anesthesia was induced in each goat with an intravenous bolus of Ketamine at 11.0 mg/kg and Diazepam at 0.5 mg/kg both given simultaneously IV. Next, animals were intubated and maintained in a plane of deep anesthesia with 3% Isoflurane and an oxygen flow rate of 11-15 ml/kg/min. A gastric tube was placed to prevent bloating. Cefazolin sodium (20 mg/kg) was administered intravenously preoperatively.
- A medial approach to the right stifle joint by osteotomy of the origin of the medial collateral ligament was taken to achieve full access to the medial meniscus. Approximately 60% of the central meniscus was excised in the red-white zone. The scaffold (+/− reinforced mesh) was secured in the defect (9×5×2 mm) using 6 interrupted PROLENE sutures (6-0) on a C-1 taper needle (FIG. 9). The joint capsule, fascial, and skin layers were closed with PROLENE-0 or VICRYL 2-0 sutures. Following the surgery, the goats were placed in a Schroeder-Thomas splint with an aluminum frame for 2 weeks to allow for partial weight bearing of the right stifle.
- The animals were sacrificed after two weeks, and the medial meniscus was removed, trimmed, and fixed in 10% neutral buffered Formalin (20× the tissue volume). The samples were processed in paraffin, cut into 5 μm sections, and stained with Hematoxylin Eosin (H & E).
- At necropsy, all implants with the embedded knitted mesh structure remained intact, whereas those without any mesh did not remain intact or were completely lost from the defect site. Furthermore, the histological sections show evidence of tissue ingrowth at the interface between the reinforced scaffolds and the native meniscus. Due to partial or complete loss of the non-reinforced foams from the defect site there was little or no tissue ingrowth into the scaffolds.
- One of ordinary skill in the art will appreciate further features and advantages of the invention based on the above-described embodiments. Accordingly, the invention is not to be limited by what has been particularly shown and described, except as indicated by the appended claims. All publications and references cited herein are expressly incorporated herein by reference in their entirety.
- What is claimed is:
Claims (53)
Priority Applications (9)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/747,488 US6852330B2 (en) | 2000-12-21 | 2000-12-21 | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US10/022,182 US20020127265A1 (en) | 2000-12-21 | 2001-12-14 | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
CA002365376A CA2365376C (en) | 2000-12-21 | 2001-12-19 | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
JP2001388080A JP4203569B2 (en) | 2000-12-21 | 2001-12-20 | Reinforced foam graft with improved structural integrity for soft tissue repair and regeneration |
DE60106183T DE60106183T2 (en) | 2000-12-21 | 2001-12-21 | Reinforced tissue implants for soft tissue repair and regeneration |
AU97396/01A AU762855B2 (en) | 2000-12-21 | 2001-12-21 | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
EP01310843A EP1216718B1 (en) | 2000-12-21 | 2001-12-21 | Reinforced foam implants for soft tissue repair and regeneration |
US10/320,751 US6884428B2 (en) | 2000-12-21 | 2002-12-16 | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US11/280,189 US8691259B2 (en) | 2000-12-21 | 2005-11-16 | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/747,488 US6852330B2 (en) | 2000-12-21 | 2000-12-21 | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/747,489 Continuation-In-Part US6599323B2 (en) | 2000-12-21 | 2000-12-21 | Reinforced tissue implants and methods of manufacture and use |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/022,182 Continuation-In-Part US20020127265A1 (en) | 2000-12-21 | 2001-12-14 | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
Publications (2)
Publication Number | Publication Date |
---|---|
US20020119177A1 true US20020119177A1 (en) | 2002-08-29 |
US6852330B2 US6852330B2 (en) | 2005-02-08 |
Family
ID=25005269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US09/747,488 Expired - Lifetime US6852330B2 (en) | 2000-12-21 | 2000-12-21 | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
Country Status (1)
Country | Link |
---|---|
US (1) | US6852330B2 (en) |
Cited By (72)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20030220700A1 (en) * | 2002-05-22 | 2003-11-27 | Hammer Joseph J. | Attachment of absorbable tissue scaffolds ot fixation devices |
US20030225459A1 (en) * | 2002-05-31 | 2003-12-04 | Hammer Joseph J. | Attachment of absorbable tissue scaffolds to fixation devices |
US20040034427A1 (en) * | 2002-08-19 | 2004-02-19 | Goel Vijay K. | Bioartificial intervertebral disc |
EP1466632A1 (en) * | 2003-04-02 | 2004-10-13 | Lifescan, Inc. | Implantable pouch seeded with insulin-producing cells to treat diabetes |
US20040249473A1 (en) * | 2003-03-28 | 2004-12-09 | Analytic Biosurgical Solutions- Abiss | Implant for treating rectocele and a device for putting said implant into place |
US20040249397A1 (en) * | 2003-03-28 | 2004-12-09 | Analytic Biosurgical Solutions- Abiss | Method and implant for curing cystocele |
US20050010306A1 (en) * | 2001-11-14 | 2005-01-13 | Jorg Priewe | Areal implant |
US20050125073A1 (en) * | 2003-12-08 | 2005-06-09 | Orban Janine M. | Implant device for cartilage regeneration in load bearing articulation regions |
US20050152880A1 (en) * | 2004-01-09 | 2005-07-14 | Regeneration Technologies, Inc. | Matrix composition for human grafts/implants |
US20050152881A1 (en) * | 2004-01-09 | 2005-07-14 | Regeneration Technologies, Inc. | Muscle-based grafts/implants |
WO2005070328A1 (en) * | 2004-01-09 | 2005-08-04 | Regeneration Technologies, Inc. | Muscle-based grafts/implants |
US20050255140A1 (en) * | 2004-05-13 | 2005-11-17 | Hagan Cary P | Methods and materials for connective tissue repair |
US20050288692A1 (en) * | 2004-06-15 | 2005-12-29 | Jean-Marc Beraud | Parietal hook |
US20060036331A1 (en) * | 2004-03-05 | 2006-02-16 | Lu Helen H | Polymer-ceramic-hydrogel composite scaffold for osteochondral repair |
US20060067969A1 (en) * | 2004-03-05 | 2006-03-30 | Lu Helen H | Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone |
US20060229721A1 (en) * | 2003-01-17 | 2006-10-12 | Ku David N | Solid implant |
WO2006116210A2 (en) * | 2005-04-25 | 2006-11-02 | Bernstein Eric F | Dermal fillers for biomedical applications in mammals and methods of using the same |
EP1743663A2 (en) * | 2005-06-29 | 2007-01-17 | Lifescan, Inc. | Multi-compartment delivery system |
US20080051809A1 (en) * | 2004-08-09 | 2008-02-28 | Verde Bvba | Implant for Treating Rotator Cuff Injuiries |
US20080071385A1 (en) * | 2003-11-26 | 2008-03-20 | Depuy Mitek, Inc. | Conformable tissue repair implant capable of injection delivery |
US20080188936A1 (en) * | 2007-02-02 | 2008-08-07 | Tornier, Inc. | System and method for repairing tendons and ligaments |
US20080220521A1 (en) * | 2004-10-25 | 2008-09-11 | Gc Corporation | Sheet for guiding regeneration of mesenchymal tissue and production method thereof |
US7611473B2 (en) | 2003-09-11 | 2009-11-03 | Ethicon, Inc. | Tissue extraction and maceration device |
US20100047309A1 (en) * | 2006-12-06 | 2010-02-25 | Lu Helen H | Graft collar and scaffold apparatuses for musculoskeletal tissue engineering and related methods |
US7763077B2 (en) | 2003-12-24 | 2010-07-27 | Biomerix Corporation | Repair of spinal annular defects and annulo-nucleoplasty regeneration |
US7803395B2 (en) | 2003-05-15 | 2010-09-28 | Biomerix Corporation | Reticulated elastomeric matrices, their manufacture and use in implantable devices |
US20100249758A1 (en) * | 2009-03-27 | 2010-09-30 | Depuy Mitek, Inc. | Methods and devices for preparing and implanting tissue scaffolds |
US7824701B2 (en) | 2002-10-18 | 2010-11-02 | Ethicon, Inc. | Biocompatible scaffold for ligament or tendon repair |
US20100292791A1 (en) * | 2007-02-12 | 2010-11-18 | Lu Helen H | Fully synthetic implantable multi-phased scaffold |
US20100318108A1 (en) * | 2009-02-02 | 2010-12-16 | Biomerix Corporation | Composite mesh devices and methods for soft tissue repair |
US7901461B2 (en) | 2003-12-05 | 2011-03-08 | Ethicon, Inc. | Viable tissue repair implants and methods of use |
US7900484B2 (en) | 2006-10-19 | 2011-03-08 | C.R. Bard, Inc. | Prosthetic repair fabric |
US7975698B2 (en) | 2004-05-21 | 2011-07-12 | Coloplast A/S | Implant for treatment of vaginal and/or uterine prolapse |
US8007430B2 (en) | 2000-10-12 | 2011-08-30 | Coloplast A/S | Apparatus and method for treating female urinary incontinence |
US8016867B2 (en) | 1999-07-23 | 2011-09-13 | Depuy Mitek, Inc. | Graft fixation device and method |
US8034003B2 (en) | 2003-09-11 | 2011-10-11 | Depuy Mitek, Inc. | Tissue extraction and collection device |
US8128554B2 (en) | 2000-10-12 | 2012-03-06 | Coloplast A/S | System for introducing a pelvic implant |
US8137686B2 (en) | 2004-04-20 | 2012-03-20 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US8167785B2 (en) | 2000-10-12 | 2012-05-01 | Coloplast A/S | Urethral support system |
US8221780B2 (en) | 2004-04-20 | 2012-07-17 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US8226715B2 (en) | 2003-06-30 | 2012-07-24 | Depuy Mitek, Inc. | Scaffold for connective tissue repair |
US8241298B2 (en) | 2009-03-27 | 2012-08-14 | Depuy Mitek, Inc. | Methods and devices for delivering and affixing tissue scaffolds |
US8449561B2 (en) | 1999-07-23 | 2013-05-28 | Depuy Mitek, Llc | Graft fixation device combination |
US8469875B2 (en) | 2000-07-05 | 2013-06-25 | Coloplast A/S | Method and device for treating urinary incontinence |
US20130211536A1 (en) * | 2010-02-18 | 2013-08-15 | Biomet Manufacturing Corporation | Method And Apparatus For Augumenting Bone Defects |
US8562542B2 (en) | 2003-03-28 | 2013-10-22 | Depuy Mitek, Llc | Tissue collection device and methods |
US8691259B2 (en) | 2000-12-21 | 2014-04-08 | Depuy Mitek, Llc | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US8709471B2 (en) | 2003-03-27 | 2014-04-29 | Coloplast A/S | Medicament delivery device and a method of medicament delivery |
US20140135811A1 (en) * | 2012-11-13 | 2014-05-15 | Covidien Lp | Occlusive devices |
US8771294B2 (en) | 2004-11-26 | 2014-07-08 | Biomerix Corporation | Aneurysm treatment devices and methods |
US8895045B2 (en) | 2003-03-07 | 2014-11-25 | Depuy Mitek, Llc | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
US9005222B2 (en) | 2002-08-02 | 2015-04-14 | Coloplast A/S | Self-anchoring sling and introducer system |
US20150320561A1 (en) * | 2014-07-17 | 2015-11-12 | Poriferous, LLC | Orbital Floor Sheet |
US9511171B2 (en) | 2002-10-18 | 2016-12-06 | Depuy Mitek, Llc | Biocompatible scaffolds with tissue fragments |
WO2017114764A1 (en) * | 2015-12-29 | 2017-07-06 | Fundación Tecnalia Research & Innovation | Uhmwpe porous polymer article, process for its production and implant and/or scaffold made thereof |
US9943390B2 (en) | 2001-03-30 | 2018-04-17 | Coloplast A/S | Method of treating pelvic organ prolapse in a female patient by accessing a prolapsed organ trans-vaginally through a vagina |
WO2019231478A1 (en) * | 2018-05-31 | 2019-12-05 | Cypris Medical, Inc. | Suture system |
CN110709111A (en) * | 2017-05-29 | 2020-01-17 | 学校法人大阪医科药科大学 | Meniscal regeneration substrate |
US10549015B2 (en) | 2014-09-24 | 2020-02-04 | Sofradim Production | Method for preparing an anti-adhesion barrier film |
US10583220B2 (en) | 2003-08-11 | 2020-03-10 | DePuy Synthes Products, Inc. | Method and apparatus for resurfacing an articular surface |
US10595979B2 (en) | 2014-02-17 | 2020-03-24 | Establishment Labs S.A. | Textured surfaces for breast implants |
US10660637B2 (en) | 2018-04-06 | 2020-05-26 | Cypris Medical, Inc. | Suturing system |
US10898181B2 (en) | 2017-03-17 | 2021-01-26 | Cypris Medical, Inc. | Suturing system |
US11045307B2 (en) | 2016-05-11 | 2021-06-29 | Establishment Labs S.A. | Medical implants and methods of preparation thereof |
US11110199B2 (en) | 2013-04-12 | 2021-09-07 | The Trustees Of Columbia University In The City Of New York | Methods for host cell homing and dental pulp regeneration |
US11202698B2 (en) | 2015-12-04 | 2021-12-21 | Establishment Labs S.A. | Textured surfaces for implants |
US11213614B2 (en) * | 2017-03-20 | 2022-01-04 | The George Washington University | Vascularized biphasic tissue constructs |
US11395865B2 (en) | 2004-02-09 | 2022-07-26 | DePuy Synthes Products, Inc. | Scaffolds with viable tissue |
US20220338974A1 (en) * | 2009-01-08 | 2022-10-27 | Rotation Medical, Inc. | Implantable tendon protection systems and related kits and methods |
US11633818B2 (en) | 2019-11-04 | 2023-04-25 | Covidien Lp | Devices, systems, and methods for treatment of intracranial aneurysms |
US11707371B2 (en) | 2008-05-13 | 2023-07-25 | Covidien Lp | Braid implant delivery systems |
US11844528B2 (en) | 2008-04-21 | 2023-12-19 | Covidien Lp | Multiple layer filamentary devices for treatment of vascular defects |
Families Citing this family (539)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2003249310A1 (en) | 2002-07-17 | 2004-02-02 | Proxy Biomedical Limited | Soft tissue implants and methods for making same |
US7066962B2 (en) * | 2002-07-23 | 2006-06-27 | Porex Surgical, Inc. | Composite surgical implant made from macroporous synthetic resin and bioglass particles |
US20040062753A1 (en) * | 2002-09-27 | 2004-04-01 | Alireza Rezania | Composite scaffolds seeded with mammalian cells |
US20050043585A1 (en) * | 2003-01-03 | 2005-02-24 | Arindam Datta | Reticulated elastomeric matrices, their manufacture and use in implantable devices |
US7368124B2 (en) * | 2003-03-07 | 2008-05-06 | Depuy Mitek, Inc. | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
EP2308423A1 (en) | 2003-04-16 | 2011-04-13 | Howmedica Osteonics Corp. | Craniofacial implant |
US8298292B2 (en) | 2003-04-16 | 2012-10-30 | Howmedica Osteonics Corp. | Craniofacial implant |
US20070084897A1 (en) | 2003-05-20 | 2007-04-19 | Shelton Frederick E Iv | Articulating surgical stapling instrument incorporating a two-piece e-beam firing mechanism |
US9060770B2 (en) | 2003-05-20 | 2015-06-23 | Ethicon Endo-Surgery, Inc. | Robotically-driven surgical instrument with E-beam driver |
KR20060130580A (en) * | 2003-12-10 | 2006-12-19 | 셀룰라 바이오엔지니어링 인코포레이티드 | Method and composition for soft tissue feature reconstruction |
ES2403357T3 (en) | 2003-12-11 | 2013-05-17 | Isto Technologies Inc. | Particle Cartilage System |
US20050165480A1 (en) * | 2004-01-23 | 2005-07-28 | Maybelle Jordan | Endovascular treatment devices and methods |
US20070190108A1 (en) * | 2004-05-17 | 2007-08-16 | Arindam Datta | High performance reticulated elastomeric matrix preparation, properties, reinforcement, and use in surgical devices, tissue augmentation and/or tissue repair |
EP3087949B1 (en) | 2004-06-14 | 2018-07-25 | Boston Scientific Limited | System relating to implantable supportive slings |
US20060086280A1 (en) * | 2004-06-15 | 2006-04-27 | Henri Duong | Anesthetic bullets using for guns and anesthetic weapons |
US8512730B2 (en) | 2004-07-12 | 2013-08-20 | Isto Technologies, Inc. | Methods of tissue repair and compositions therefor |
US9072535B2 (en) | 2011-05-27 | 2015-07-07 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments with rotatable staple deployment arrangements |
US11896225B2 (en) | 2004-07-28 | 2024-02-13 | Cilag Gmbh International | Staple cartridge comprising a pan |
US8215531B2 (en) | 2004-07-28 | 2012-07-10 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument having a medical substance dispenser |
US11998198B2 (en) | 2004-07-28 | 2024-06-04 | Cilag Gmbh International | Surgical stapling instrument incorporating a two-piece E-beam firing mechanism |
US7351423B2 (en) * | 2004-09-01 | 2008-04-01 | Depuy Spine, Inc. | Musculo-skeletal implant having a bioactive gradient |
US8263102B2 (en) | 2004-09-28 | 2012-09-11 | Atrium Medical Corporation | Drug delivery coating for use with a stent |
US9012506B2 (en) | 2004-09-28 | 2015-04-21 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US8312836B2 (en) * | 2004-09-28 | 2012-11-20 | Atrium Medical Corporation | Method and apparatus for application of a fresh coating on a medical device |
US8367099B2 (en) | 2004-09-28 | 2013-02-05 | Atrium Medical Corporation | Perforated fatty acid films |
US9000040B2 (en) | 2004-09-28 | 2015-04-07 | Atrium Medical Corporation | Cross-linked fatty acid-based biomaterials |
US9801982B2 (en) * | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Implantable barrier device |
US9801913B2 (en) * | 2004-09-28 | 2017-10-31 | Atrium Medical Corporation | Barrier layer |
US20090011116A1 (en) * | 2004-09-28 | 2009-01-08 | Atrium Medical Corporation | Reducing template with coating receptacle containing a medical device to be coated |
US20060116713A1 (en) * | 2004-11-26 | 2006-06-01 | Ivan Sepetka | Aneurysm treatment devices and methods |
US20060116714A1 (en) * | 2004-11-26 | 2006-06-01 | Ivan Sepetka | Coupling and release devices and methods for their assembly and use |
ES2449196T3 (en) | 2005-04-06 | 2014-03-18 | Boston Scientific Limited | Suburethral support set |
US8263109B2 (en) * | 2005-05-09 | 2012-09-11 | Boston Scientific Scimed, Inc. | Injectable bulking compositions |
EP1909687A1 (en) | 2005-07-13 | 2008-04-16 | Boston Scientific Scimed, Inc. | Snap fit sling anchor system and related methods |
US7878969B2 (en) | 2005-07-25 | 2011-02-01 | Boston Scientific Scimed, Inc. | Pelvic floor repair system |
US20070036842A1 (en) * | 2005-08-15 | 2007-02-15 | Concordia Manufacturing Llc | Non-woven scaffold for tissue engineering |
JP5292533B2 (en) | 2005-08-26 | 2013-09-18 | ジンマー・インコーポレイテッド | Implant and joint disease treatment, replacement and treatment methods |
US9237891B2 (en) | 2005-08-31 | 2016-01-19 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical stapling devices that produce formed staples having different lengths |
US7934630B2 (en) | 2005-08-31 | 2011-05-03 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US7669746B2 (en) | 2005-08-31 | 2010-03-02 | Ethicon Endo-Surgery, Inc. | Staple cartridges for forming staples having differing formed staple heights |
US10159482B2 (en) | 2005-08-31 | 2018-12-25 | Ethicon Llc | Fastener cartridge assembly comprising a fixed anvil and different staple heights |
US11484312B2 (en) | 2005-08-31 | 2022-11-01 | Cilag Gmbh International | Staple cartridge comprising a staple driver arrangement |
US11246590B2 (en) | 2005-08-31 | 2022-02-15 | Cilag Gmbh International | Staple cartridge including staple drivers having different unfired heights |
US8936805B2 (en) | 2005-09-09 | 2015-01-20 | Board Of Trustees Of The University Of Arkansas | Bone regeneration using biodegradable polymeric nanocomposite materials and applications of the same |
US8518123B2 (en) * | 2005-09-09 | 2013-08-27 | Board Of Trustees Of The University Of Arkansas | System and method for tissue generation and bone regeneration |
US9763788B2 (en) | 2005-09-09 | 2017-09-19 | Board Of Trustees Of The University Of Arkansas | Bone regeneration using biodegradable polymeric nanocomposite materials and applications of the same |
WO2007070141A1 (en) | 2005-09-12 | 2007-06-21 | Proxy Biomedical Limited | Soft tissue implants and methods for making same |
US9278161B2 (en) | 2005-09-28 | 2016-03-08 | Atrium Medical Corporation | Tissue-separating fatty acid adhesion barrier |
US9427423B2 (en) | 2009-03-10 | 2016-08-30 | Atrium Medical Corporation | Fatty-acid based particles |
US9005646B2 (en) | 2005-10-12 | 2015-04-14 | Lifenet Health | Compositions for repair of defects in tissues, and methods of making the same |
US9132208B2 (en) * | 2008-08-07 | 2015-09-15 | Lifenet Health | Composition for a tissue repair implant and methods of making the same |
CA2626030A1 (en) | 2005-10-15 | 2007-04-26 | Atrium Medical Corporation | Hydrophobic cross-linked gels for bioabsorbable drug carrier coatings |
US20070106317A1 (en) | 2005-11-09 | 2007-05-10 | Shelton Frederick E Iv | Hydraulically and electrically actuated articulation joints for surgical instruments |
US20070128243A1 (en) * | 2005-12-02 | 2007-06-07 | Xylos Corporation | Implantable microbial cellulose materials for various medical applications |
US7513865B2 (en) * | 2005-12-20 | 2009-04-07 | Boston Scientific Scimed, Inc. | Flattened tubular mesh sling and related methods |
US8820603B2 (en) | 2006-01-31 | 2014-09-02 | Ethicon Endo-Surgery, Inc. | Accessing data stored in a memory of a surgical instrument |
US11793518B2 (en) | 2006-01-31 | 2023-10-24 | Cilag Gmbh International | Powered surgical instruments with firing system lockout arrangements |
US11224427B2 (en) | 2006-01-31 | 2022-01-18 | Cilag Gmbh International | Surgical stapling system including a console and retraction assembly |
US20120292367A1 (en) | 2006-01-31 | 2012-11-22 | Ethicon Endo-Surgery, Inc. | Robotically-controlled end effector |
US20110290856A1 (en) | 2006-01-31 | 2011-12-01 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical instrument with force-feedback capabilities |
US8186555B2 (en) | 2006-01-31 | 2012-05-29 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting and fastening instrument with mechanical closure system |
US7845537B2 (en) | 2006-01-31 | 2010-12-07 | Ethicon Endo-Surgery, Inc. | Surgical instrument having recording capabilities |
US20110024477A1 (en) | 2009-02-06 | 2011-02-03 | Hall Steven G | Driven Surgical Stapler Improvements |
US7753904B2 (en) | 2006-01-31 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Endoscopic surgical instrument with a handle that can articulate with respect to the shaft |
US11278279B2 (en) | 2006-01-31 | 2022-03-22 | Cilag Gmbh International | Surgical instrument assembly |
US8708213B2 (en) | 2006-01-31 | 2014-04-29 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a feedback system |
US7709631B2 (en) | 2006-03-13 | 2010-05-04 | Xylos Corporation | Oxidized microbial cellulose and use thereof |
US8992422B2 (en) | 2006-03-23 | 2015-03-31 | Ethicon Endo-Surgery, Inc. | Robotically-controlled endoscopic accessory channel |
US8721519B2 (en) | 2006-06-06 | 2014-05-13 | Boston Scientific Scimed, Inc. | Implantable mesh combining biodegradable and non-biodegradable fibers |
US20070286884A1 (en) * | 2006-06-13 | 2007-12-13 | Xylos Corporation | Implantable microbial cellulose materials for hard tissue repair and regeneration |
US8322455B2 (en) | 2006-06-27 | 2012-12-04 | Ethicon Endo-Surgery, Inc. | Manually driven surgical cutting and fastening instrument |
US8220690B2 (en) | 2006-09-29 | 2012-07-17 | Ethicon Endo-Surgery, Inc. | Connected surgical staples and stapling instruments for deploying the same |
US10568652B2 (en) | 2006-09-29 | 2020-02-25 | Ethicon Llc | Surgical staples having attached drivers of different heights and stapling instruments for deploying the same |
US11980366B2 (en) | 2006-10-03 | 2024-05-14 | Cilag Gmbh International | Surgical instrument |
EP2076218B1 (en) | 2006-10-09 | 2016-03-09 | Active Implants Corporation | Meniscus prosthetic device |
US8192491B2 (en) * | 2006-10-09 | 2012-06-05 | Active Implants Corporation | Meniscus prosthetic device |
US9492596B2 (en) * | 2006-11-06 | 2016-11-15 | Atrium Medical Corporation | Barrier layer with underlying medical device and one or more reinforcing support structures |
WO2008057328A2 (en) * | 2006-11-06 | 2008-05-15 | Atrium Medical Corporation | Tissue separating device with reinforced support for anchoring mechanisms |
US8628553B2 (en) * | 2006-11-08 | 2014-01-14 | Ethicon Endo-Surgery, Inc. | Expanding adhesive foam structure to reduce stomach volume |
WO2008074027A1 (en) * | 2006-12-13 | 2008-06-19 | Biomerix Corporation | Aneurysm occlusion devices |
US8163549B2 (en) | 2006-12-20 | 2012-04-24 | Zimmer Orthobiologics, Inc. | Method of obtaining viable small tissue particles and use for tissue repair |
US8632535B2 (en) | 2007-01-10 | 2014-01-21 | Ethicon Endo-Surgery, Inc. | Interlock and surgical instrument including same |
US8684253B2 (en) | 2007-01-10 | 2014-04-01 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between a control unit of a robotic system and remote sensor |
US8652120B2 (en) | 2007-01-10 | 2014-02-18 | Ethicon Endo-Surgery, Inc. | Surgical instrument with wireless communication between control unit and sensor transponders |
US11291441B2 (en) | 2007-01-10 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with wireless communication between control unit and remote sensor |
US7434717B2 (en) | 2007-01-11 | 2008-10-14 | Ethicon Endo-Surgery, Inc. | Apparatus for closing a curved anvil of a surgical stapling device |
US11039836B2 (en) | 2007-01-11 | 2021-06-22 | Cilag Gmbh International | Staple cartridge for use with a surgical stapling instrument |
US7604151B2 (en) | 2007-03-15 | 2009-10-20 | Ethicon Endo-Surgery, Inc. | Surgical stapling systems and staple cartridges for deploying surgical staples with tissue compression features |
US8893946B2 (en) | 2007-03-28 | 2014-11-25 | Ethicon Endo-Surgery, Inc. | Laparoscopic tissue thickness and clamp load measuring devices |
US20080255665A1 (en) * | 2007-04-11 | 2008-10-16 | Active Implants Corporation | Anchored prosthetic meniscus device |
CA2684040C (en) * | 2007-04-12 | 2016-12-06 | Isto Technologies, Inc. | Method of forming an implant using a mold that mimics the shape of the tissue defect site and implant formed therefrom |
US11857181B2 (en) | 2007-06-04 | 2024-01-02 | Cilag Gmbh International | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US8931682B2 (en) | 2007-06-04 | 2015-01-13 | Ethicon Endo-Surgery, Inc. | Robotically-controlled shaft based rotary drive systems for surgical instruments |
US7753245B2 (en) | 2007-06-22 | 2010-07-13 | Ethicon Endo-Surgery, Inc. | Surgical stapling instruments |
US20090004455A1 (en) * | 2007-06-27 | 2009-01-01 | Philippe Gravagna | Reinforced composite implant |
US11849941B2 (en) | 2007-06-29 | 2023-12-26 | Cilag Gmbh International | Staple cartridge having staple cavities extending at a transverse angle relative to a longitudinal cartridge axis |
US20090018655A1 (en) * | 2007-07-13 | 2009-01-15 | John Brunelle | Composite Implant for Surgical Repair |
US7998380B2 (en) * | 2007-07-13 | 2011-08-16 | Wisconsin Alumni Research Foundation | Method of fabricating a tissue engineering scaffold |
US20100198354A1 (en) | 2007-08-01 | 2010-08-05 | Jeffrey Halbrecht | Method and system for patella tendon realignment |
US20100131069A1 (en) * | 2007-08-01 | 2010-05-27 | Jeffrey Halbrecht | Method and system for patella tendon realignment |
US9308068B2 (en) * | 2007-12-03 | 2016-04-12 | Sofradim Production | Implant for parastomal hernia |
EP2070557A1 (en) | 2007-12-12 | 2009-06-17 | Xylos Corporation | Implantable microbial cellulose materials for hard tissue repair and regeneration |
US20090157193A1 (en) * | 2007-12-18 | 2009-06-18 | Warsaw Orthopedic, Inc. | Tendon and Ligament Repair Sheet and Methods of Use |
US8758391B2 (en) | 2008-02-14 | 2014-06-24 | Ethicon Endo-Surgery, Inc. | Interchangeable tools for surgical instruments |
US9179912B2 (en) | 2008-02-14 | 2015-11-10 | Ethicon Endo-Surgery, Inc. | Robotically-controlled motorized surgical cutting and fastening instrument |
US8636736B2 (en) | 2008-02-14 | 2014-01-28 | Ethicon Endo-Surgery, Inc. | Motorized surgical cutting and fastening instrument |
US7866527B2 (en) | 2008-02-14 | 2011-01-11 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with interlockable firing system |
US11986183B2 (en) | 2008-02-14 | 2024-05-21 | Cilag Gmbh International | Surgical cutting and fastening instrument comprising a plurality of sensors to measure an electrical parameter |
JP5410110B2 (en) | 2008-02-14 | 2014-02-05 | エシコン・エンド−サージェリィ・インコーポレイテッド | Surgical cutting / fixing instrument with RF electrode |
US7819298B2 (en) | 2008-02-14 | 2010-10-26 | Ethicon Endo-Surgery, Inc. | Surgical stapling apparatus with control features operable with one hand |
US8573465B2 (en) | 2008-02-14 | 2013-11-05 | Ethicon Endo-Surgery, Inc. | Robotically-controlled surgical end effector system with rotary actuated closure systems |
US11272927B2 (en) | 2008-02-15 | 2022-03-15 | Cilag Gmbh International | Layer arrangements for surgical staple cartridges |
US9770245B2 (en) | 2008-02-15 | 2017-09-26 | Ethicon Llc | Layer arrangements for surgical staple cartridges |
US7991599B2 (en) | 2008-04-09 | 2011-08-02 | Active Implants Corporation | Meniscus prosthetic device selection and implantation methods |
US7611653B1 (en) * | 2008-04-09 | 2009-11-03 | Active Implants Corporation | Manufacturing and material processing for prosthetic devices |
US8016884B2 (en) | 2008-04-09 | 2011-09-13 | Active Implants Corporation | Tensioned meniscus prosthetic devices and associated methods |
US8361147B2 (en) | 2008-04-09 | 2013-01-29 | Active Implants Corporation | Meniscus prosthetic devices with anti-migration features |
WO2009125402A2 (en) | 2008-04-10 | 2009-10-15 | Bonus Therapeutics Ltd | Bone-like prosthetic implants |
WO2009156866A2 (en) | 2008-06-27 | 2009-12-30 | Sofradim Production | Biosynthetic implant for soft tissue repair |
US9387280B2 (en) * | 2008-09-05 | 2016-07-12 | Synovis Orthopedic And Woundcare, Inc. | Device for soft tissue repair or replacement |
US8210411B2 (en) | 2008-09-23 | 2012-07-03 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument |
US9386983B2 (en) | 2008-09-23 | 2016-07-12 | Ethicon Endo-Surgery, Llc | Robotically-controlled motorized surgical instrument |
US9005230B2 (en) | 2008-09-23 | 2015-04-14 | Ethicon Endo-Surgery, Inc. | Motorized surgical instrument |
US11648005B2 (en) | 2008-09-23 | 2023-05-16 | Cilag Gmbh International | Robotically-controlled motorized surgical instrument with an end effector |
US8608045B2 (en) | 2008-10-10 | 2013-12-17 | Ethicon Endo-Sugery, Inc. | Powered surgical cutting and stapling apparatus with manually retractable firing system |
WO2010051256A1 (en) * | 2008-10-27 | 2010-05-06 | Sessions Pharmaceuticals Inc. | Fluid extracting wound dressing |
US8517239B2 (en) | 2009-02-05 | 2013-08-27 | Ethicon Endo-Surgery, Inc. | Surgical stapling instrument comprising a magnetic element driver |
EP2393430A1 (en) | 2009-02-06 | 2011-12-14 | Ethicon Endo-Surgery, Inc. | Driven surgical stapler improvements |
US8444036B2 (en) | 2009-02-06 | 2013-05-21 | Ethicon Endo-Surgery, Inc. | Motor driven surgical fastener device with mechanisms for adjusting a tissue gap within the end effector |
US8801801B2 (en) * | 2009-04-03 | 2014-08-12 | Biomerix Corporation | At least partially resorbable reticulated elastomeric matrix elements and methods of making same |
CN101574542B (en) * | 2009-06-22 | 2012-09-12 | 张朝跃 | Compound material for internal fixation of tendons carrying transgenic cells and preparation method thereof |
US20110038910A1 (en) | 2009-08-11 | 2011-02-17 | Atrium Medical Corporation | Anti-infective antimicrobial-containing biomaterials |
US9278004B2 (en) | 2009-08-27 | 2016-03-08 | Cotera, Inc. | Method and apparatus for altering biomechanics of the articular joints |
US9668868B2 (en) | 2009-08-27 | 2017-06-06 | Cotera, Inc. | Apparatus and methods for treatment of patellofemoral conditions |
US9861408B2 (en) | 2009-08-27 | 2018-01-09 | The Foundry, Llc | Method and apparatus for treating canine cruciate ligament disease |
US10349980B2 (en) | 2009-08-27 | 2019-07-16 | The Foundry, Llc | Method and apparatus for altering biomechanics of the shoulder |
CN105615966B (en) | 2009-08-27 | 2019-08-23 | 科特拉有限公司 | Equipment for treating joint to carry out power distribution in the joint |
US8377432B2 (en) * | 2009-09-02 | 2013-02-19 | Khay-Yong Saw | Method and composition for neochondrogenesis |
FR2949688B1 (en) | 2009-09-04 | 2012-08-24 | Sofradim Production | FABRIC WITH PICOTS COATED WITH A BIORESORBABLE MICROPOROUS LAYER |
US8690960B2 (en) * | 2009-11-24 | 2014-04-08 | Covidien Lp | Reinforced tissue patch |
US9398943B2 (en) * | 2009-11-30 | 2016-07-26 | Covidien Lp | Ventral hernia repair with barbed suture |
US8220688B2 (en) | 2009-12-24 | 2012-07-17 | Ethicon Endo-Surgery, Inc. | Motor-driven surgical cutting instrument with electric actuator directional control assembly |
US8851354B2 (en) | 2009-12-24 | 2014-10-07 | Ethicon Endo-Surgery, Inc. | Surgical cutting instrument that analyzes tissue thickness |
EP2593141B1 (en) | 2010-07-16 | 2018-07-04 | Atrium Medical Corporation | Composition and methods for altering the rate of hydrolysis of cured oil-based materials |
US8783543B2 (en) | 2010-07-30 | 2014-07-22 | Ethicon Endo-Surgery, Inc. | Tissue acquisition arrangements and methods for surgical stapling devices |
US11812965B2 (en) | 2010-09-30 | 2023-11-14 | Cilag Gmbh International | Layer of material for a surgical end effector |
US9555171B2 (en) | 2010-09-30 | 2017-01-31 | Depuy Mitek, Llc | Methods and devices for collecting separate components of whole blood |
US9839420B2 (en) | 2010-09-30 | 2017-12-12 | Ethicon Llc | Tissue thickness compensator comprising at least one medicament |
US9629814B2 (en) | 2010-09-30 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator configured to redistribute compressive forces |
US9517063B2 (en) | 2012-03-28 | 2016-12-13 | Ethicon Endo-Surgery, Llc | Movable member for use with a tissue thickness compensator |
US10213198B2 (en) | 2010-09-30 | 2019-02-26 | Ethicon Llc | Actuator for releasing a tissue thickness compensator from a fastener cartridge |
US9364233B2 (en) | 2010-09-30 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Tissue thickness compensators for circular surgical staplers |
US11298125B2 (en) | 2010-09-30 | 2022-04-12 | Cilag Gmbh International | Tissue stapler having a thickness compensator |
US9320523B2 (en) | 2012-03-28 | 2016-04-26 | Ethicon Endo-Surgery, Llc | Tissue thickness compensator comprising tissue ingrowth features |
US11849952B2 (en) | 2010-09-30 | 2023-12-26 | Cilag Gmbh International | Staple cartridge comprising staples positioned within a compressible portion thereof |
US10945731B2 (en) | 2010-09-30 | 2021-03-16 | Ethicon Llc | Tissue thickness compensator comprising controlled release and expansion |
US9168038B2 (en) | 2010-09-30 | 2015-10-27 | Ethicon Endo-Surgery, Inc. | Staple cartridge comprising a tissue thickness compensator |
US8695866B2 (en) | 2010-10-01 | 2014-04-15 | Ethicon Endo-Surgery, Inc. | Surgical instrument having a power control circuit |
US8551525B2 (en) | 2010-12-23 | 2013-10-08 | Biostructures, Llc | Bone graft materials and methods |
WO2012097381A1 (en) | 2011-01-14 | 2012-07-19 | Biomerix Corporation | At least partially resorbable reticulated elastomeric matrix elements and methods of making same |
US8691126B2 (en) | 2011-01-18 | 2014-04-08 | Wisconsin Alumni Research Foundation | Method of fabricating an injection molded component |
FR2972626B1 (en) | 2011-03-16 | 2014-04-11 | Sofradim Production | PROSTHETIC COMPRISING A THREE-DIMENSIONAL KNIT AND ADJUSTED |
US9017711B2 (en) | 2011-04-28 | 2015-04-28 | Warsaw Orthopedic, Inc. | Soft tissue wrap |
JP6026509B2 (en) | 2011-04-29 | 2016-11-16 | エシコン・エンド−サージェリィ・インコーポレイテッドEthicon Endo−Surgery,Inc. | Staple cartridge including staples disposed within a compressible portion of the staple cartridge itself |
US9113991B2 (en) | 2011-05-12 | 2015-08-25 | Boston Scientific Scimed, Inc. | Anchors for bodily implants and methods for anchoring bodily implants into a patient's body |
US9636201B2 (en) | 2011-05-12 | 2017-05-02 | Boston Scientific Scimed, Inc. | Delivery members for delivering an implant into a body of a patient |
US11207064B2 (en) | 2011-05-27 | 2021-12-28 | Cilag Gmbh International | Automated end effector component reloading system for use with a robotic system |
FR2977789B1 (en) | 2011-07-13 | 2013-07-19 | Sofradim Production | PROSTHETIC FOR UMBILIC HERNIA |
FR2977790B1 (en) | 2011-07-13 | 2013-07-19 | Sofradim Production | PROSTHETIC FOR UMBILIC HERNIA |
EP2760494B1 (en) | 2011-09-30 | 2017-04-19 | Sofradim Production | Reversible stiffening of light weight mesh |
FR2985271B1 (en) | 2011-12-29 | 2014-01-24 | Sofradim Production | KNITTED PICOTS |
FR2985170B1 (en) | 2011-12-29 | 2014-01-24 | Sofradim Production | PROSTHESIS FOR INGUINAL HERNIA |
US9044230B2 (en) | 2012-02-13 | 2015-06-02 | Ethicon Endo-Surgery, Inc. | Surgical cutting and fastening instrument with apparatus for determining cartridge and firing motion status |
CN104334098B (en) | 2012-03-28 | 2017-03-22 | 伊西康内外科公司 | Tissue thickness compensator comprising capsules defining a low pressure environment |
RU2644272C2 (en) | 2012-03-28 | 2018-02-08 | Этикон Эндо-Серджери, Инк. | Limitation node with tissue thickness compensator |
MX358135B (en) | 2012-03-28 | 2018-08-06 | Ethicon Endo Surgery Inc | Tissue thickness compensator comprising a plurality of layers. |
US9867880B2 (en) | 2012-06-13 | 2018-01-16 | Atrium Medical Corporation | Cured oil-hydrogel biomaterial compositions for controlled drug delivery |
US9101358B2 (en) | 2012-06-15 | 2015-08-11 | Ethicon Endo-Surgery, Inc. | Articulatable surgical instrument comprising a firing drive |
US9282974B2 (en) | 2012-06-28 | 2016-03-15 | Ethicon Endo-Surgery, Llc | Empty clip cartridge lockout |
US9364230B2 (en) | 2012-06-28 | 2016-06-14 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with rotary joint assemblies |
US11278284B2 (en) | 2012-06-28 | 2022-03-22 | Cilag Gmbh International | Rotary drive arrangements for surgical instruments |
BR112014032776B1 (en) | 2012-06-28 | 2021-09-08 | Ethicon Endo-Surgery, Inc | SURGICAL INSTRUMENT SYSTEM AND SURGICAL KIT FOR USE WITH A SURGICAL INSTRUMENT SYSTEM |
US9289256B2 (en) | 2012-06-28 | 2016-03-22 | Ethicon Endo-Surgery, Llc | Surgical end effectors having angled tissue-contacting surfaces |
RU2636861C2 (en) | 2012-06-28 | 2017-11-28 | Этикон Эндо-Серджери, Инк. | Blocking of empty cassette with clips |
US20140005718A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Multi-functional powered surgical device with external dissection features |
US20140001231A1 (en) | 2012-06-28 | 2014-01-02 | Ethicon Endo-Surgery, Inc. | Firing system lockout arrangements for surgical instruments |
FR2994185B1 (en) | 2012-08-02 | 2015-07-31 | Sofradim Production | PROCESS FOR THE PREPARATION OF A POROUS CHITOSAN LAYER |
US9468466B1 (en) | 2012-08-24 | 2016-10-18 | Cotera, Inc. | Method and apparatus for altering biomechanics of the spine |
FR2995788B1 (en) | 2012-09-25 | 2014-09-26 | Sofradim Production | HEMOSTATIC PATCH AND PREPARATION METHOD |
FR2995779B1 (en) | 2012-09-25 | 2015-09-25 | Sofradim Production | PROSTHETIC COMPRISING A TREILLIS AND A MEANS OF CONSOLIDATION |
FR2995778B1 (en) | 2012-09-25 | 2015-06-26 | Sofradim Production | ABDOMINAL WALL REINFORCING PROSTHESIS AND METHOD FOR MANUFACTURING THE SAME |
EP2900174B1 (en) | 2012-09-28 | 2017-04-12 | Sofradim Production | Packaging for a hernia repair device |
US10245306B2 (en) | 2012-11-16 | 2019-04-02 | Isto Technologies Ii, Llc | Flexible tissue matrix and methods for joint repair |
US20140178343A1 (en) | 2012-12-21 | 2014-06-26 | Jian Q. Yao | Supports and methods for promoting integration of cartilage tissue explants |
JP6382235B2 (en) | 2013-03-01 | 2018-08-29 | エシコン・エンド−サージェリィ・インコーポレイテッドEthicon Endo−Surgery,Inc. | Articulatable surgical instrument with a conductive path for signal communication |
BR112015021082B1 (en) | 2013-03-01 | 2022-05-10 | Ethicon Endo-Surgery, Inc | surgical instrument |
US9630346B2 (en) | 2013-03-05 | 2017-04-25 | Wisconsin Alumni Research Foundation | Method of fabricating an injection molded component |
US9629623B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgery, Llc | Drive system lockout arrangements for modular surgical instruments |
US9629629B2 (en) | 2013-03-14 | 2017-04-25 | Ethicon Endo-Surgey, LLC | Control systems for surgical instruments |
US10136887B2 (en) | 2013-04-16 | 2018-11-27 | Ethicon Llc | Drive system decoupling arrangement for a surgical instrument |
BR112015026109B1 (en) | 2013-04-16 | 2022-02-22 | Ethicon Endo-Surgery, Inc | surgical instrument |
WO2014179720A1 (en) | 2013-05-02 | 2014-11-06 | University Of South Florida | Implantable sonic windows |
FR3006578B1 (en) | 2013-06-07 | 2015-05-29 | Sofradim Production | PROSTHESIS BASED ON TEXTILE FOR LAPAROSCOPIC PATHWAY |
FR3006581B1 (en) | 2013-06-07 | 2016-07-22 | Sofradim Production | PROSTHESIS BASED ON TEXTILE FOR LAPAROSCOPIC PATHWAY |
US9808249B2 (en) | 2013-08-23 | 2017-11-07 | Ethicon Llc | Attachment portions for surgical instrument assemblies |
RU2678363C2 (en) | 2013-08-23 | 2019-01-28 | ЭТИКОН ЭНДО-СЕРДЖЕРИ, ЭлЭлСи | Firing member retraction devices for powered surgical instruments |
US9555564B2 (en) | 2013-11-11 | 2017-01-31 | Wisconsin Alumni Research Foundation | Method of fabricating a foamed, injection molded component with improved ductility and toughness |
AT515384B1 (en) * | 2014-02-05 | 2016-04-15 | Dietmar Dr Sonnleitner | Preconnected multilayer film for covering a bone defect site |
US9962161B2 (en) | 2014-02-12 | 2018-05-08 | Ethicon Llc | Deliverable surgical instrument |
BR112016019387B1 (en) | 2014-02-24 | 2022-11-29 | Ethicon Endo-Surgery, Llc | SURGICAL INSTRUMENT SYSTEM AND FASTENER CARTRIDGE FOR USE WITH A SURGICAL FIXING INSTRUMENT |
US10028761B2 (en) | 2014-03-26 | 2018-07-24 | Ethicon Llc | Feedback algorithms for manual bailout systems for surgical instruments |
US20150272557A1 (en) | 2014-03-26 | 2015-10-01 | Ethicon Endo-Surgery, Inc. | Modular surgical instrument system |
BR112016021943B1 (en) | 2014-03-26 | 2022-06-14 | Ethicon Endo-Surgery, Llc | SURGICAL INSTRUMENT FOR USE BY AN OPERATOR IN A SURGICAL PROCEDURE |
US9804618B2 (en) | 2014-03-26 | 2017-10-31 | Ethicon Llc | Systems and methods for controlling a segmented circuit |
EP3129075A4 (en) | 2014-04-10 | 2017-12-06 | Bonus Therapeutics Ltd. | Bone repair compositions |
BR112016023807B1 (en) | 2014-04-16 | 2022-07-12 | Ethicon Endo-Surgery, Llc | CARTRIDGE SET OF FASTENERS FOR USE WITH A SURGICAL INSTRUMENT |
US10206677B2 (en) | 2014-09-26 | 2019-02-19 | Ethicon Llc | Surgical staple and driver arrangements for staple cartridges |
US10470768B2 (en) | 2014-04-16 | 2019-11-12 | Ethicon Llc | Fastener cartridge including a layer attached thereto |
US20150297225A1 (en) | 2014-04-16 | 2015-10-22 | Ethicon Endo-Surgery, Inc. | Fastener cartridges including extensions having different configurations |
BR112016023698B1 (en) | 2014-04-16 | 2022-07-26 | Ethicon Endo-Surgery, Llc | FASTENER CARTRIDGE FOR USE WITH A SURGICAL INSTRUMENT |
CN106456158B (en) | 2014-04-16 | 2019-02-05 | 伊西康内外科有限责任公司 | Fastener cartridge including non-uniform fastener |
EP3148599B1 (en) | 2014-05-30 | 2019-12-18 | Sofradim Production | Method for preparing neutralized matrix of non-antigenic collagenous material |
US11311294B2 (en) | 2014-09-05 | 2022-04-26 | Cilag Gmbh International | Powered medical device including measurement of closure state of jaws |
BR112017004361B1 (en) | 2014-09-05 | 2023-04-11 | Ethicon Llc | ELECTRONIC SYSTEM FOR A SURGICAL INSTRUMENT |
US9757128B2 (en) | 2014-09-05 | 2017-09-12 | Ethicon Llc | Multiple sensors with one sensor affecting a second sensor's output or interpretation |
US10105142B2 (en) | 2014-09-18 | 2018-10-23 | Ethicon Llc | Surgical stapler with plurality of cutting elements |
BR112017005981B1 (en) | 2014-09-26 | 2022-09-06 | Ethicon, Llc | ANCHOR MATERIAL FOR USE WITH A SURGICAL STAPLE CARTRIDGE AND SURGICAL STAPLE CARTRIDGE FOR USE WITH A SURGICAL INSTRUMENT |
US11523821B2 (en) | 2014-09-26 | 2022-12-13 | Cilag Gmbh International | Method for creating a flexible staple line |
EP3000433B1 (en) | 2014-09-29 | 2022-09-21 | Sofradim Production | Device for introducing a prosthesis for hernia treatment into an incision and flexible textile based prosthesis |
EP3000432B1 (en) | 2014-09-29 | 2022-05-04 | Sofradim Production | Textile-based prosthesis for treatment of inguinal hernia |
US10179191B2 (en) | 2014-10-09 | 2019-01-15 | Isto Technologies Ii, Llc | Flexible tissue matrix and methods for joint repair |
US10076325B2 (en) | 2014-10-13 | 2018-09-18 | Ethicon Llc | Surgical stapling apparatus comprising a tissue stop |
US9924944B2 (en) | 2014-10-16 | 2018-03-27 | Ethicon Llc | Staple cartridge comprising an adjunct material |
US10517594B2 (en) | 2014-10-29 | 2019-12-31 | Ethicon Llc | Cartridge assemblies for surgical staplers |
US11141153B2 (en) | 2014-10-29 | 2021-10-12 | Cilag Gmbh International | Staple cartridges comprising driver arrangements |
US9844376B2 (en) | 2014-11-06 | 2017-12-19 | Ethicon Llc | Staple cartridge comprising a releasable adjunct material |
EP3029189B1 (en) | 2014-12-05 | 2021-08-11 | Sofradim Production | Prosthetic porous knit, method of making same and hernia prosthesis |
US10736636B2 (en) | 2014-12-10 | 2020-08-11 | Ethicon Llc | Articulatable surgical instrument system |
US10085748B2 (en) | 2014-12-18 | 2018-10-02 | Ethicon Llc | Locking arrangements for detachable shaft assemblies with articulatable surgical end effectors |
MX2017008108A (en) | 2014-12-18 | 2018-03-06 | Ethicon Llc | Surgical instrument with an anvil that is selectively movable about a discrete non-movable axis relative to a staple cartridge. |
US10188385B2 (en) | 2014-12-18 | 2019-01-29 | Ethicon Llc | Surgical instrument system comprising lockable systems |
US9987000B2 (en) | 2014-12-18 | 2018-06-05 | Ethicon Llc | Surgical instrument assembly comprising a flexible articulation system |
US9844375B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Drive arrangements for articulatable surgical instruments |
US9844374B2 (en) | 2014-12-18 | 2017-12-19 | Ethicon Llc | Surgical instrument systems comprising an articulatable end effector and means for adjusting the firing stroke of a firing member |
US9968355B2 (en) | 2014-12-18 | 2018-05-15 | Ethicon Llc | Surgical instruments with articulatable end effectors and improved firing beam support arrangements |
EP3059255B1 (en) | 2015-02-17 | 2020-05-13 | Sofradim Production | Method for preparing a chitosan-based matrix comprising a fiber reinforcement member |
US10321907B2 (en) | 2015-02-27 | 2019-06-18 | Ethicon Llc | System for monitoring whether a surgical instrument needs to be serviced |
US11154301B2 (en) | 2015-02-27 | 2021-10-26 | Cilag Gmbh International | Modular stapling assembly |
US10180463B2 (en) | 2015-02-27 | 2019-01-15 | Ethicon Llc | Surgical apparatus configured to assess whether a performance parameter of the surgical apparatus is within an acceptable performance band |
JP2020121162A (en) | 2015-03-06 | 2020-08-13 | エシコン エルエルシーEthicon LLC | Time dependent evaluation of sensor data to determine stability element, creep element and viscoelastic element of measurement |
US10052044B2 (en) | 2015-03-06 | 2018-08-21 | Ethicon Llc | Time dependent evaluation of sensor data to determine stability, creep, and viscoelastic elements of measures |
US9993248B2 (en) | 2015-03-06 | 2018-06-12 | Ethicon Endo-Surgery, Llc | Smart sensors with local signal processing |
US9808246B2 (en) | 2015-03-06 | 2017-11-07 | Ethicon Endo-Surgery, Llc | Method of operating a powered surgical instrument |
US9924961B2 (en) | 2015-03-06 | 2018-03-27 | Ethicon Endo-Surgery, Llc | Interactive feedback system for powered surgical instruments |
US10617412B2 (en) | 2015-03-06 | 2020-04-14 | Ethicon Llc | System for detecting the mis-insertion of a staple cartridge into a surgical stapler |
US9901342B2 (en) | 2015-03-06 | 2018-02-27 | Ethicon Endo-Surgery, Llc | Signal and power communication system positioned on a rotatable shaft |
US10245033B2 (en) | 2015-03-06 | 2019-04-02 | Ethicon Llc | Surgical instrument comprising a lockable battery housing |
US10441279B2 (en) | 2015-03-06 | 2019-10-15 | Ethicon Llc | Multiple level thresholds to modify operation of powered surgical instruments |
US10687806B2 (en) | 2015-03-06 | 2020-06-23 | Ethicon Llc | Adaptive tissue compression techniques to adjust closure rates for multiple tissue types |
US10213201B2 (en) | 2015-03-31 | 2019-02-26 | Ethicon Llc | Stapling end effector configured to compensate for an uneven gap between a first jaw and a second jaw |
EP3085337B1 (en) | 2015-04-24 | 2022-09-14 | Sofradim Production | Prosthesis for supporting a breast structure |
ES2676072T3 (en) | 2015-06-19 | 2018-07-16 | Sofradim Production | Synthetic prosthesis comprising a knitted fabric and a non-porous film and method of forming it |
CA2938576A1 (en) | 2015-08-12 | 2017-02-12 | Howmedica Osteonics Corp. | Methods for forming scaffolds |
US11331191B2 (en) | 2015-08-12 | 2022-05-17 | Howmedica Osteonics Corp. | Bioactive soft tissue implant and methods of manufacture and use thereof |
US11058425B2 (en) * | 2015-08-17 | 2021-07-13 | Ethicon Llc | Implantable layers for a surgical instrument |
US10363036B2 (en) | 2015-09-23 | 2019-07-30 | Ethicon Llc | Surgical stapler having force-based motor control |
US10238386B2 (en) | 2015-09-23 | 2019-03-26 | Ethicon Llc | Surgical stapler having motor control based on an electrical parameter related to a motor current |
US10327769B2 (en) | 2015-09-23 | 2019-06-25 | Ethicon Llc | Surgical stapler having motor control based on a drive system component |
US10105139B2 (en) | 2015-09-23 | 2018-10-23 | Ethicon Llc | Surgical stapler having downstream current-based motor control |
US10299878B2 (en) | 2015-09-25 | 2019-05-28 | Ethicon Llc | Implantable adjunct systems for determining adjunct skew |
US11890015B2 (en) | 2015-09-30 | 2024-02-06 | Cilag Gmbh International | Compressible adjunct with crossing spacer fibers |
US10980539B2 (en) | 2015-09-30 | 2021-04-20 | Ethicon Llc | Implantable adjunct comprising bonded layers |
US10524788B2 (en) | 2015-09-30 | 2020-01-07 | Ethicon Llc | Compressible adjunct with attachment regions |
US10736633B2 (en) | 2015-09-30 | 2020-08-11 | Ethicon Llc | Compressible adjunct with looping members |
US9925298B2 (en) | 2015-10-27 | 2018-03-27 | Council Of Scientific & Industrial Research | Porous polymer scaffold useful for tissue engineering in stem cell transplantation |
US10292704B2 (en) | 2015-12-30 | 2019-05-21 | Ethicon Llc | Mechanisms for compensating for battery pack failure in powered surgical instruments |
US10368865B2 (en) | 2015-12-30 | 2019-08-06 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10265068B2 (en) | 2015-12-30 | 2019-04-23 | Ethicon Llc | Surgical instruments with separable motors and motor control circuits |
EP3195830B1 (en) | 2016-01-25 | 2020-11-18 | Sofradim Production | Prosthesis for hernia repair |
US11213293B2 (en) | 2016-02-09 | 2022-01-04 | Cilag Gmbh International | Articulatable surgical instruments with single articulation link arrangements |
US10245029B2 (en) | 2016-02-09 | 2019-04-02 | Ethicon Llc | Surgical instrument with articulating and axially translatable end effector |
BR112018016098B1 (en) | 2016-02-09 | 2023-02-23 | Ethicon Llc | SURGICAL INSTRUMENT |
US11224426B2 (en) | 2016-02-12 | 2022-01-18 | Cilag Gmbh International | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10448948B2 (en) | 2016-02-12 | 2019-10-22 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10258331B2 (en) | 2016-02-12 | 2019-04-16 | Ethicon Llc | Mechanisms for compensating for drivetrain failure in powered surgical instruments |
US10485542B2 (en) | 2016-04-01 | 2019-11-26 | Ethicon Llc | Surgical stapling instrument comprising multiple lockouts |
US10617413B2 (en) | 2016-04-01 | 2020-04-14 | Ethicon Llc | Closure system arrangements for surgical cutting and stapling devices with separate and distinct firing shafts |
US10492783B2 (en) | 2016-04-15 | 2019-12-03 | Ethicon, Llc | Surgical instrument with improved stop/start control during a firing motion |
US10828028B2 (en) | 2016-04-15 | 2020-11-10 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10357247B2 (en) | 2016-04-15 | 2019-07-23 | Ethicon Llc | Surgical instrument with multiple program responses during a firing motion |
US10456137B2 (en) | 2016-04-15 | 2019-10-29 | Ethicon Llc | Staple formation detection mechanisms |
US11179150B2 (en) | 2016-04-15 | 2021-11-23 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US11607239B2 (en) | 2016-04-15 | 2023-03-21 | Cilag Gmbh International | Systems and methods for controlling a surgical stapling and cutting instrument |
US10426467B2 (en) | 2016-04-15 | 2019-10-01 | Ethicon Llc | Surgical instrument with detection sensors |
US10335145B2 (en) | 2016-04-15 | 2019-07-02 | Ethicon Llc | Modular surgical instrument with configurable operating mode |
US10405859B2 (en) | 2016-04-15 | 2019-09-10 | Ethicon Llc | Surgical instrument with adjustable stop/start control during a firing motion |
US11317917B2 (en) | 2016-04-18 | 2022-05-03 | Cilag Gmbh International | Surgical stapling system comprising a lockable firing assembly |
US20170296173A1 (en) | 2016-04-18 | 2017-10-19 | Ethicon Endo-Surgery, Llc | Method for operating a surgical instrument |
US10368867B2 (en) | 2016-04-18 | 2019-08-06 | Ethicon Llc | Surgical instrument comprising a lockout |
EP3241571B1 (en) | 2016-05-02 | 2020-07-22 | Howmedica Osteonics Corporation | Bioactive soft tissue implant and methods of manufacture and use thereof |
CN109689893A (en) | 2016-07-11 | 2019-04-26 | 博纳斯治疗公司 | Cell composition for regeneration |
EP3312325B1 (en) | 2016-10-21 | 2021-09-22 | Sofradim Production | Method for forming a mesh having a barbed suture attached thereto and the mesh thus obtained |
US10524789B2 (en) | 2016-12-21 | 2020-01-07 | Ethicon Llc | Laterally actuatable articulation lock arrangements for locking an end effector of a surgical instrument in an articulated configuration |
US10499914B2 (en) | 2016-12-21 | 2019-12-10 | Ethicon Llc | Staple forming pocket arrangements |
US20180168615A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Method of deforming staples from two different types of staple cartridges with the same surgical stapling instrument |
US11090048B2 (en) | 2016-12-21 | 2021-08-17 | Cilag Gmbh International | Method for resetting a fuse of a surgical instrument shaft |
MX2019007295A (en) | 2016-12-21 | 2019-10-15 | Ethicon Llc | Surgical instrument system comprising an end effector lockout and a firing assembly lockout. |
US10568624B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Surgical instruments with jaws that are pivotable about a fixed axis and include separate and distinct closure and firing systems |
US10639035B2 (en) | 2016-12-21 | 2020-05-05 | Ethicon Llc | Surgical stapling instruments and replaceable tool assemblies thereof |
US10881401B2 (en) | 2016-12-21 | 2021-01-05 | Ethicon Llc | Staple firing member comprising a missing cartridge and/or spent cartridge lockout |
US11134942B2 (en) | 2016-12-21 | 2021-10-05 | Cilag Gmbh International | Surgical stapling instruments and staple-forming anvils |
US10624635B2 (en) | 2016-12-21 | 2020-04-21 | Ethicon Llc | Firing members with non-parallel jaw engagement features for surgical end effectors |
US10856868B2 (en) | 2016-12-21 | 2020-12-08 | Ethicon Llc | Firing member pin configurations |
US20180168608A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Surgical instrument system comprising an end effector lockout and a firing assembly lockout |
US20180168625A1 (en) | 2016-12-21 | 2018-06-21 | Ethicon Endo-Surgery, Llc | Surgical stapling instruments with smart staple cartridges |
US11419606B2 (en) | 2016-12-21 | 2022-08-23 | Cilag Gmbh International | Shaft assembly comprising a clutch configured to adapt the output of a rotary firing member to two different systems |
US10568625B2 (en) | 2016-12-21 | 2020-02-25 | Ethicon Llc | Staple cartridges and arrangements of staples and staple cavities therein |
BR112019011947A2 (en) | 2016-12-21 | 2019-10-29 | Ethicon Llc | surgical stapling systems |
JP7010956B2 (en) | 2016-12-21 | 2022-01-26 | エシコン エルエルシー | How to staple tissue |
CN110099619B (en) | 2016-12-21 | 2022-07-15 | 爱惜康有限责任公司 | Lockout device for surgical end effector and replaceable tool assembly |
US10426471B2 (en) | 2016-12-21 | 2019-10-01 | Ethicon Llc | Surgical instrument with multiple failure response modes |
US10542982B2 (en) | 2016-12-21 | 2020-01-28 | Ethicon Llc | Shaft assembly comprising first and second articulation lockouts |
EP3398554A1 (en) | 2017-05-02 | 2018-11-07 | Sofradim Production | Prosthesis for inguinal hernia repair |
US10624633B2 (en) | 2017-06-20 | 2020-04-21 | Ethicon Llc | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument |
USD879808S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with graphical user interface |
US10307170B2 (en) | 2017-06-20 | 2019-06-04 | Ethicon Llc | Method for closed loop control of motor velocity of a surgical stapling and cutting instrument |
US11382638B2 (en) | 2017-06-20 | 2022-07-12 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified displacement distance |
US10327767B2 (en) | 2017-06-20 | 2019-06-25 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
USD879809S1 (en) | 2017-06-20 | 2020-03-31 | Ethicon Llc | Display panel with changeable graphical user interface |
US11517325B2 (en) | 2017-06-20 | 2022-12-06 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured displacement distance traveled over a specified time interval |
US10368864B2 (en) | 2017-06-20 | 2019-08-06 | Ethicon Llc | Systems and methods for controlling displaying motor velocity for a surgical instrument |
US10881396B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Surgical instrument with variable duration trigger arrangement |
US10888321B2 (en) | 2017-06-20 | 2021-01-12 | Ethicon Llc | Systems and methods for controlling velocity of a displacement member of a surgical stapling and cutting instrument |
US10980537B2 (en) | 2017-06-20 | 2021-04-20 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on measured time over a specified number of shaft rotations |
US10779820B2 (en) | 2017-06-20 | 2020-09-22 | Ethicon Llc | Systems and methods for controlling motor speed according to user input for a surgical instrument |
US11071554B2 (en) | 2017-06-20 | 2021-07-27 | Cilag Gmbh International | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on magnitude of velocity error measurements |
US11653914B2 (en) | 2017-06-20 | 2023-05-23 | Cilag Gmbh International | Systems and methods for controlling motor velocity of a surgical stapling and cutting instrument according to articulation angle of end effector |
US10881399B2 (en) | 2017-06-20 | 2021-01-05 | Ethicon Llc | Techniques for adaptive control of motor velocity of a surgical stapling and cutting instrument |
US10390841B2 (en) | 2017-06-20 | 2019-08-27 | Ethicon Llc | Control of motor velocity of a surgical stapling and cutting instrument based on angle of articulation |
US10646220B2 (en) | 2017-06-20 | 2020-05-12 | Ethicon Llc | Systems and methods for controlling displacement member velocity for a surgical instrument |
USD890784S1 (en) | 2017-06-20 | 2020-07-21 | Ethicon Llc | Display panel with changeable graphical user interface |
US11090046B2 (en) | 2017-06-20 | 2021-08-17 | Cilag Gmbh International | Systems and methods for controlling displacement member motion of a surgical stapling and cutting instrument |
US10813639B2 (en) | 2017-06-20 | 2020-10-27 | Ethicon Llc | Closed loop feedback control of motor velocity of a surgical stapling and cutting instrument based on system conditions |
US11324503B2 (en) | 2017-06-27 | 2022-05-10 | Cilag Gmbh International | Surgical firing member arrangements |
US11266405B2 (en) | 2017-06-27 | 2022-03-08 | Cilag Gmbh International | Surgical anvil manufacturing methods |
US10856869B2 (en) | 2017-06-27 | 2020-12-08 | Ethicon Llc | Surgical anvil arrangements |
US11141154B2 (en) | 2017-06-27 | 2021-10-12 | Cilag Gmbh International | Surgical end effectors and anvils |
US10993716B2 (en) | 2017-06-27 | 2021-05-04 | Ethicon Llc | Surgical anvil arrangements |
US10772629B2 (en) | 2017-06-27 | 2020-09-15 | Ethicon Llc | Surgical anvil arrangements |
USD851762S1 (en) | 2017-06-28 | 2019-06-18 | Ethicon Llc | Anvil |
US11564686B2 (en) | 2017-06-28 | 2023-01-31 | Cilag Gmbh International | Surgical shaft assemblies with flexible interfaces |
US10716614B2 (en) | 2017-06-28 | 2020-07-21 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies with increased contact pressure |
USD906355S1 (en) | 2017-06-28 | 2020-12-29 | Ethicon Llc | Display screen or portion thereof with a graphical user interface for a surgical instrument |
US11246592B2 (en) | 2017-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical instrument comprising an articulation system lockable to a frame |
USD869655S1 (en) | 2017-06-28 | 2019-12-10 | Ethicon Llc | Surgical fastener cartridge |
EP3420947B1 (en) | 2017-06-28 | 2022-05-25 | Cilag GmbH International | Surgical instrument comprising selectively actuatable rotatable couplers |
US10903685B2 (en) | 2017-06-28 | 2021-01-26 | Ethicon Llc | Surgical shaft assemblies with slip ring assemblies forming capacitive channels |
US11259805B2 (en) | 2017-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical instrument comprising firing member supports |
US20190000459A1 (en) | 2017-06-28 | 2019-01-03 | Ethicon Llc | Surgical instruments with jaws constrained to pivot about an axis upon contact with a closure member that is parked in close proximity to the pivot axis |
USD854151S1 (en) | 2017-06-28 | 2019-07-16 | Ethicon Llc | Surgical instrument shaft |
US10211586B2 (en) | 2017-06-28 | 2019-02-19 | Ethicon Llc | Surgical shaft assemblies with watertight housings |
US10765427B2 (en) | 2017-06-28 | 2020-09-08 | Ethicon Llc | Method for articulating a surgical instrument |
US11389161B2 (en) | 2017-06-28 | 2022-07-19 | Cilag Gmbh International | Surgical instrument comprising selectively actuatable rotatable couplers |
US10898183B2 (en) | 2017-06-29 | 2021-01-26 | Ethicon Llc | Robotic surgical instrument with closed loop feedback techniques for advancement of closure member during firing |
US10398434B2 (en) | 2017-06-29 | 2019-09-03 | Ethicon Llc | Closed loop velocity control of closure member for robotic surgical instrument |
US10258418B2 (en) | 2017-06-29 | 2019-04-16 | Ethicon Llc | System for controlling articulation forces |
US11007022B2 (en) | 2017-06-29 | 2021-05-18 | Ethicon Llc | Closed loop velocity control techniques based on sensed tissue parameters for robotic surgical instrument |
US10932772B2 (en) | 2017-06-29 | 2021-03-02 | Ethicon Llc | Methods for closed loop velocity control for robotic surgical instrument |
US11471155B2 (en) | 2017-08-03 | 2022-10-18 | Cilag Gmbh International | Surgical system bailout |
US11304695B2 (en) | 2017-08-03 | 2022-04-19 | Cilag Gmbh International | Surgical system shaft interconnection |
US11974742B2 (en) | 2017-08-03 | 2024-05-07 | Cilag Gmbh International | Surgical system comprising an articulation bailout |
US11944300B2 (en) | 2017-08-03 | 2024-04-02 | Cilag Gmbh International | Method for operating a surgical system bailout |
US10796471B2 (en) | 2017-09-29 | 2020-10-06 | Ethicon Llc | Systems and methods of displaying a knife position for a surgical instrument |
US10743872B2 (en) | 2017-09-29 | 2020-08-18 | Ethicon Llc | System and methods for controlling a display of a surgical instrument |
US10729501B2 (en) | 2017-09-29 | 2020-08-04 | Ethicon Llc | Systems and methods for language selection of a surgical instrument |
USD907648S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
USD917500S1 (en) | 2017-09-29 | 2021-04-27 | Ethicon Llc | Display screen or portion thereof with graphical user interface |
USD907647S1 (en) | 2017-09-29 | 2021-01-12 | Ethicon Llc | Display screen or portion thereof with animated graphical user interface |
US10765429B2 (en) | 2017-09-29 | 2020-09-08 | Ethicon Llc | Systems and methods for providing alerts according to the operational state of a surgical instrument |
US11399829B2 (en) | 2017-09-29 | 2022-08-02 | Cilag Gmbh International | Systems and methods of initiating a power shutdown mode for a surgical instrument |
US11134944B2 (en) | 2017-10-30 | 2021-10-05 | Cilag Gmbh International | Surgical stapler knife motion controls |
US11090075B2 (en) | 2017-10-30 | 2021-08-17 | Cilag Gmbh International | Articulation features for surgical end effector |
US10842490B2 (en) | 2017-10-31 | 2020-11-24 | Ethicon Llc | Cartridge body design with force reduction based on firing completion |
US10779903B2 (en) | 2017-10-31 | 2020-09-22 | Ethicon Llc | Positive shaft rotation lock activated by jaw closure |
US10828033B2 (en) | 2017-12-15 | 2020-11-10 | Ethicon Llc | Handheld electromechanical surgical instruments with improved motor control arrangements for positioning components of an adapter coupled thereto |
US11033267B2 (en) | 2017-12-15 | 2021-06-15 | Ethicon Llc | Systems and methods of controlling a clamping member firing rate of a surgical instrument |
US10869666B2 (en) | 2017-12-15 | 2020-12-22 | Ethicon Llc | Adapters with control systems for controlling multiple motors of an electromechanical surgical instrument |
US10966718B2 (en) | 2017-12-15 | 2021-04-06 | Ethicon Llc | Dynamic clamping assemblies with improved wear characteristics for use in connection with electromechanical surgical instruments |
US10687813B2 (en) | 2017-12-15 | 2020-06-23 | Ethicon Llc | Adapters with firing stroke sensing arrangements for use in connection with electromechanical surgical instruments |
US10743875B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Surgical end effectors with jaw stiffener arrangements configured to permit monitoring of firing member |
US10779826B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Methods of operating surgical end effectors |
US10779825B2 (en) | 2017-12-15 | 2020-09-22 | Ethicon Llc | Adapters with end effector position sensing and control arrangements for use in connection with electromechanical surgical instruments |
US11197670B2 (en) | 2017-12-15 | 2021-12-14 | Cilag Gmbh International | Surgical end effectors with pivotal jaws configured to touch at their respective distal ends when fully closed |
US11071543B2 (en) | 2017-12-15 | 2021-07-27 | Cilag Gmbh International | Surgical end effectors with clamping assemblies configured to increase jaw aperture ranges |
US11006955B2 (en) | 2017-12-15 | 2021-05-18 | Ethicon Llc | End effectors with positive jaw opening features for use with adapters for electromechanical surgical instruments |
US10743874B2 (en) | 2017-12-15 | 2020-08-18 | Ethicon Llc | Sealed adapters for use with electromechanical surgical instruments |
US11045270B2 (en) | 2017-12-19 | 2021-06-29 | Cilag Gmbh International | Robotic attachment comprising exterior drive actuator |
US10835330B2 (en) | 2017-12-19 | 2020-11-17 | Ethicon Llc | Method for determining the position of a rotatable jaw of a surgical instrument attachment assembly |
US11020112B2 (en) | 2017-12-19 | 2021-06-01 | Ethicon Llc | Surgical tools configured for interchangeable use with different controller interfaces |
US10729509B2 (en) | 2017-12-19 | 2020-08-04 | Ethicon Llc | Surgical instrument comprising closure and firing locking mechanism |
USD910847S1 (en) | 2017-12-19 | 2021-02-16 | Ethicon Llc | Surgical instrument assembly |
US10716565B2 (en) | 2017-12-19 | 2020-07-21 | Ethicon Llc | Surgical instruments with dual articulation drivers |
US11129680B2 (en) | 2017-12-21 | 2021-09-28 | Cilag Gmbh International | Surgical instrument comprising a projector |
US11311290B2 (en) | 2017-12-21 | 2022-04-26 | Cilag Gmbh International | Surgical instrument comprising an end effector dampener |
US11337691B2 (en) | 2017-12-21 | 2022-05-24 | Cilag Gmbh International | Surgical instrument configured to determine firing path |
US11076853B2 (en) | 2017-12-21 | 2021-08-03 | Cilag Gmbh International | Systems and methods of displaying a knife position during transection for a surgical instrument |
US11998654B2 (en) | 2018-07-12 | 2024-06-04 | Bard Shannon Limited | Securing implants and medical devices |
US11039834B2 (en) | 2018-08-20 | 2021-06-22 | Cilag Gmbh International | Surgical stapler anvils with staple directing protrusions and tissue stability features |
US10912559B2 (en) | 2018-08-20 | 2021-02-09 | Ethicon Llc | Reinforced deformable anvil tip for surgical stapler anvil |
US10779821B2 (en) | 2018-08-20 | 2020-09-22 | Ethicon Llc | Surgical stapler anvils with tissue stop features configured to avoid tissue pinch |
US10842492B2 (en) | 2018-08-20 | 2020-11-24 | Ethicon Llc | Powered articulatable surgical instruments with clutching and locking arrangements for linking an articulation drive system to a firing drive system |
US11324501B2 (en) | 2018-08-20 | 2022-05-10 | Cilag Gmbh International | Surgical stapling devices with improved closure members |
USD914878S1 (en) | 2018-08-20 | 2021-03-30 | Ethicon Llc | Surgical instrument anvil |
US11207065B2 (en) | 2018-08-20 | 2021-12-28 | Cilag Gmbh International | Method for fabricating surgical stapler anvils |
US10856870B2 (en) | 2018-08-20 | 2020-12-08 | Ethicon Llc | Switching arrangements for motor powered articulatable surgical instruments |
US11291440B2 (en) | 2018-08-20 | 2022-04-05 | Cilag Gmbh International | Method for operating a powered articulatable surgical instrument |
US11083458B2 (en) | 2018-08-20 | 2021-08-10 | Cilag Gmbh International | Powered surgical instruments with clutching arrangements to convert linear drive motions to rotary drive motions |
US11253256B2 (en) | 2018-08-20 | 2022-02-22 | Cilag Gmbh International | Articulatable motor powered surgical instruments with dedicated articulation motor arrangements |
US11045192B2 (en) | 2018-08-20 | 2021-06-29 | Cilag Gmbh International | Fabricating techniques for surgical stapler anvils |
EP3653171A1 (en) | 2018-11-16 | 2020-05-20 | Sofradim Production | Implants suitable for soft tissue repair |
US11147551B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11172929B2 (en) | 2019-03-25 | 2021-11-16 | Cilag Gmbh International | Articulation drive arrangements for surgical systems |
US11147553B2 (en) | 2019-03-25 | 2021-10-19 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11696761B2 (en) | 2019-03-25 | 2023-07-11 | Cilag Gmbh International | Firing drive arrangements for surgical systems |
US11471157B2 (en) | 2019-04-30 | 2022-10-18 | Cilag Gmbh International | Articulation control mapping for a surgical instrument |
US11452528B2 (en) | 2019-04-30 | 2022-09-27 | Cilag Gmbh International | Articulation actuators for a surgical instrument |
US11903581B2 (en) | 2019-04-30 | 2024-02-20 | Cilag Gmbh International | Methods for stapling tissue using a surgical instrument |
US11432816B2 (en) | 2019-04-30 | 2022-09-06 | Cilag Gmbh International | Articulation pin for a surgical instrument |
US11253254B2 (en) | 2019-04-30 | 2022-02-22 | Cilag Gmbh International | Shaft rotation actuator on a surgical instrument |
US11648009B2 (en) | 2019-04-30 | 2023-05-16 | Cilag Gmbh International | Rotatable jaw tip for a surgical instrument |
US11426251B2 (en) | 2019-04-30 | 2022-08-30 | Cilag Gmbh International | Articulation directional lights on a surgical instrument |
US11298132B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Inlernational | Staple cartridge including a honeycomb extension |
US11224497B2 (en) | 2019-06-28 | 2022-01-18 | Cilag Gmbh International | Surgical systems with multiple RFID tags |
US11684434B2 (en) | 2019-06-28 | 2023-06-27 | Cilag Gmbh International | Surgical RFID assemblies for instrument operational setting control |
US11051807B2 (en) | 2019-06-28 | 2021-07-06 | Cilag Gmbh International | Packaging assembly including a particulate trap |
US11478241B2 (en) | 2019-06-28 | 2022-10-25 | Cilag Gmbh International | Staple cartridge including projections |
US11219455B2 (en) | 2019-06-28 | 2022-01-11 | Cilag Gmbh International | Surgical instrument including a lockout key |
US11259803B2 (en) | 2019-06-28 | 2022-03-01 | Cilag Gmbh International | Surgical stapling system having an information encryption protocol |
US11246678B2 (en) | 2019-06-28 | 2022-02-15 | Cilag Gmbh International | Surgical stapling system having a frangible RFID tag |
US11291451B2 (en) | 2019-06-28 | 2022-04-05 | Cilag Gmbh International | Surgical instrument with battery compatibility verification functionality |
US11523822B2 (en) | 2019-06-28 | 2022-12-13 | Cilag Gmbh International | Battery pack including a circuit interrupter |
US11771419B2 (en) | 2019-06-28 | 2023-10-03 | Cilag Gmbh International | Packaging for a replaceable component of a surgical stapling system |
US11298127B2 (en) | 2019-06-28 | 2022-04-12 | Cilag GmbH Interational | Surgical stapling system having a lockout mechanism for an incompatible cartridge |
US11627959B2 (en) | 2019-06-28 | 2023-04-18 | Cilag Gmbh International | Surgical instruments including manual and powered system lockouts |
US11553971B2 (en) | 2019-06-28 | 2023-01-17 | Cilag Gmbh International | Surgical RFID assemblies for display and communication |
US11660163B2 (en) | 2019-06-28 | 2023-05-30 | Cilag Gmbh International | Surgical system with RFID tags for updating motor assembly parameters |
US11426167B2 (en) | 2019-06-28 | 2022-08-30 | Cilag Gmbh International | Mechanisms for proper anvil attachment surgical stapling head assembly |
US11350938B2 (en) | 2019-06-28 | 2022-06-07 | Cilag Gmbh International | Surgical instrument comprising an aligned rfid sensor |
US11497492B2 (en) | 2019-06-28 | 2022-11-15 | Cilag Gmbh International | Surgical instrument including an articulation lock |
US12004740B2 (en) | 2019-06-28 | 2024-06-11 | Cilag Gmbh International | Surgical stapling system having an information decryption protocol |
US11376098B2 (en) | 2019-06-28 | 2022-07-05 | Cilag Gmbh International | Surgical instrument system comprising an RFID system |
US11399837B2 (en) | 2019-06-28 | 2022-08-02 | Cilag Gmbh International | Mechanisms for motor control adjustments of a motorized surgical instrument |
US11638587B2 (en) | 2019-06-28 | 2023-05-02 | Cilag Gmbh International | RFID identification systems for surgical instruments |
US11464601B2 (en) | 2019-06-28 | 2022-10-11 | Cilag Gmbh International | Surgical instrument comprising an RFID system for tracking a movable component |
US11529139B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Motor driven surgical instrument |
US11844520B2 (en) | 2019-12-19 | 2023-12-19 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11701111B2 (en) | 2019-12-19 | 2023-07-18 | Cilag Gmbh International | Method for operating a surgical stapling instrument |
US11464512B2 (en) | 2019-12-19 | 2022-10-11 | Cilag Gmbh International | Staple cartridge comprising a curved deck surface |
US11607219B2 (en) | 2019-12-19 | 2023-03-21 | Cilag Gmbh International | Staple cartridge comprising a detachable tissue cutting knife |
US11291447B2 (en) | 2019-12-19 | 2022-04-05 | Cilag Gmbh International | Stapling instrument comprising independent jaw closing and staple firing systems |
US11931033B2 (en) | 2019-12-19 | 2024-03-19 | Cilag Gmbh International | Staple cartridge comprising a latch lockout |
US11234698B2 (en) | 2019-12-19 | 2022-02-01 | Cilag Gmbh International | Stapling system comprising a clamp lockout and a firing lockout |
US11576672B2 (en) | 2019-12-19 | 2023-02-14 | Cilag Gmbh International | Surgical instrument comprising a closure system including a closure member and an opening member driven by a drive screw |
US11529137B2 (en) | 2019-12-19 | 2022-12-20 | Cilag Gmbh International | Staple cartridge comprising driver retention members |
US11446029B2 (en) | 2019-12-19 | 2022-09-20 | Cilag Gmbh International | Staple cartridge comprising projections extending from a curved deck surface |
US11911032B2 (en) | 2019-12-19 | 2024-02-27 | Cilag Gmbh International | Staple cartridge comprising a seating cam |
US11304696B2 (en) | 2019-12-19 | 2022-04-19 | Cilag Gmbh International | Surgical instrument comprising a powered articulation system |
US11504122B2 (en) | 2019-12-19 | 2022-11-22 | Cilag Gmbh International | Surgical instrument comprising a nested firing member |
US12035913B2 (en) | 2019-12-19 | 2024-07-16 | Cilag Gmbh International | Staple cartridge comprising a deployable knife |
US11559304B2 (en) | 2019-12-19 | 2023-01-24 | Cilag Gmbh International | Surgical instrument comprising a rapid closure mechanism |
WO2021138081A1 (en) | 2020-01-02 | 2021-07-08 | Zkr Orthopedics, Inc. | Patella tendon realignment implant with changeable shape |
WO2021163317A1 (en) | 2020-02-11 | 2021-08-19 | Embody, Inc. | Surgical cannula with removable pressure seal |
CA3170125A1 (en) | 2020-02-11 | 2021-08-19 | Embody, Inc. | Implant delivery device |
CA3170127A1 (en) | 2020-02-11 | 2021-08-19 | Embody, Inc. | Surgical anchoring device, deployment device, and method of use |
USD975851S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD966512S1 (en) | 2020-06-02 | 2022-10-11 | Cilag Gmbh International | Staple cartridge |
USD967421S1 (en) | 2020-06-02 | 2022-10-18 | Cilag Gmbh International | Staple cartridge |
USD975850S1 (en) | 2020-06-02 | 2023-01-17 | Cilag Gmbh International | Staple cartridge |
USD975278S1 (en) | 2020-06-02 | 2023-01-10 | Cilag Gmbh International | Staple cartridge |
USD974560S1 (en) | 2020-06-02 | 2023-01-03 | Cilag Gmbh International | Staple cartridge |
USD976401S1 (en) | 2020-06-02 | 2023-01-24 | Cilag Gmbh International | Staple cartridge |
US20220031320A1 (en) | 2020-07-28 | 2022-02-03 | Cilag Gmbh International | Surgical instruments with flexible firing member actuator constraint arrangements |
US11452526B2 (en) | 2020-10-29 | 2022-09-27 | Cilag Gmbh International | Surgical instrument comprising a staged voltage regulation start-up system |
US11534259B2 (en) | 2020-10-29 | 2022-12-27 | Cilag Gmbh International | Surgical instrument comprising an articulation indicator |
US11931025B2 (en) | 2020-10-29 | 2024-03-19 | Cilag Gmbh International | Surgical instrument comprising a releasable closure drive lock |
US11896217B2 (en) | 2020-10-29 | 2024-02-13 | Cilag Gmbh International | Surgical instrument comprising an articulation lock |
US11517390B2 (en) | 2020-10-29 | 2022-12-06 | Cilag Gmbh International | Surgical instrument comprising a limited travel switch |
US11779330B2 (en) | 2020-10-29 | 2023-10-10 | Cilag Gmbh International | Surgical instrument comprising a jaw alignment system |
US11844518B2 (en) | 2020-10-29 | 2023-12-19 | Cilag Gmbh International | Method for operating a surgical instrument |
US11717289B2 (en) | 2020-10-29 | 2023-08-08 | Cilag Gmbh International | Surgical instrument comprising an indicator which indicates that an articulation drive is actuatable |
US11617577B2 (en) | 2020-10-29 | 2023-04-04 | Cilag Gmbh International | Surgical instrument comprising a sensor configured to sense whether an articulation drive of the surgical instrument is actuatable |
USD980425S1 (en) | 2020-10-29 | 2023-03-07 | Cilag Gmbh International | Surgical instrument assembly |
USD1013170S1 (en) | 2020-10-29 | 2024-01-30 | Cilag Gmbh International | Surgical instrument assembly |
US11653915B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Surgical instruments with sled location detection and adjustment features |
US11737751B2 (en) | 2020-12-02 | 2023-08-29 | Cilag Gmbh International | Devices and methods of managing energy dissipated within sterile barriers of surgical instrument housings |
US11849943B2 (en) | 2020-12-02 | 2023-12-26 | Cilag Gmbh International | Surgical instrument with cartridge release mechanisms |
US11744581B2 (en) | 2020-12-02 | 2023-09-05 | Cilag Gmbh International | Powered surgical instruments with multi-phase tissue treatment |
US11890010B2 (en) | 2020-12-02 | 2024-02-06 | Cllag GmbH International | Dual-sided reinforced reload for surgical instruments |
US11627960B2 (en) | 2020-12-02 | 2023-04-18 | Cilag Gmbh International | Powered surgical instruments with smart reload with separately attachable exteriorly mounted wiring connections |
US11653920B2 (en) | 2020-12-02 | 2023-05-23 | Cilag Gmbh International | Powered surgical instruments with communication interfaces through sterile barrier |
US11944296B2 (en) | 2020-12-02 | 2024-04-02 | Cilag Gmbh International | Powered surgical instruments with external connectors |
US11678882B2 (en) | 2020-12-02 | 2023-06-20 | Cilag Gmbh International | Surgical instruments with interactive features to remedy incidental sled movements |
US11744583B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Distal communication array to tune frequency of RF systems |
US11812964B2 (en) | 2021-02-26 | 2023-11-14 | Cilag Gmbh International | Staple cartridge comprising a power management circuit |
US11925349B2 (en) | 2021-02-26 | 2024-03-12 | Cilag Gmbh International | Adjustment to transfer parameters to improve available power |
US11730473B2 (en) | 2021-02-26 | 2023-08-22 | Cilag Gmbh International | Monitoring of manufacturing life-cycle |
US11749877B2 (en) | 2021-02-26 | 2023-09-05 | Cilag Gmbh International | Stapling instrument comprising a signal antenna |
US11793514B2 (en) | 2021-02-26 | 2023-10-24 | Cilag Gmbh International | Staple cartridge comprising sensor array which may be embedded in cartridge body |
US11751869B2 (en) | 2021-02-26 | 2023-09-12 | Cilag Gmbh International | Monitoring of multiple sensors over time to detect moving characteristics of tissue |
US11980362B2 (en) | 2021-02-26 | 2024-05-14 | Cilag Gmbh International | Surgical instrument system comprising a power transfer coil |
US11723657B2 (en) | 2021-02-26 | 2023-08-15 | Cilag Gmbh International | Adjustable communication based on available bandwidth and power capacity |
US11950779B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Method of powering and communicating with a staple cartridge |
US11701113B2 (en) | 2021-02-26 | 2023-07-18 | Cilag Gmbh International | Stapling instrument comprising a separate power antenna and a data transfer antenna |
US11950777B2 (en) | 2021-02-26 | 2024-04-09 | Cilag Gmbh International | Staple cartridge comprising an information access control system |
US11696757B2 (en) | 2021-02-26 | 2023-07-11 | Cilag Gmbh International | Monitoring of internal systems to detect and track cartridge motion status |
US11737749B2 (en) | 2021-03-22 | 2023-08-29 | Cilag Gmbh International | Surgical stapling instrument comprising a retraction system |
US11826012B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Stapling instrument comprising a pulsed motor-driven firing rack |
US11826042B2 (en) | 2021-03-22 | 2023-11-28 | Cilag Gmbh International | Surgical instrument comprising a firing drive including a selectable leverage mechanism |
US11717291B2 (en) | 2021-03-22 | 2023-08-08 | Cilag Gmbh International | Staple cartridge comprising staples configured to apply different tissue compression |
US11806011B2 (en) | 2021-03-22 | 2023-11-07 | Cilag Gmbh International | Stapling instrument comprising tissue compression systems |
US11723658B2 (en) | 2021-03-22 | 2023-08-15 | Cilag Gmbh International | Staple cartridge comprising a firing lockout |
US11759202B2 (en) | 2021-03-22 | 2023-09-19 | Cilag Gmbh International | Staple cartridge comprising an implantable layer |
US11832816B2 (en) | 2021-03-24 | 2023-12-05 | Cilag Gmbh International | Surgical stapling assembly comprising nonplanar staples and planar staples |
US11896219B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Mating features between drivers and underside of a cartridge deck |
US11903582B2 (en) | 2021-03-24 | 2024-02-20 | Cilag Gmbh International | Leveraging surfaces for cartridge installation |
US11849944B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Drivers for fastener cartridge assemblies having rotary drive screws |
US11944336B2 (en) | 2021-03-24 | 2024-04-02 | Cilag Gmbh International | Joint arrangements for multi-planar alignment and support of operational drive shafts in articulatable surgical instruments |
US11857183B2 (en) | 2021-03-24 | 2024-01-02 | Cilag Gmbh International | Stapling assembly components having metal substrates and plastic bodies |
US11896218B2 (en) | 2021-03-24 | 2024-02-13 | Cilag Gmbh International | Method of using a powered stapling device |
US11793516B2 (en) | 2021-03-24 | 2023-10-24 | Cilag Gmbh International | Surgical staple cartridge comprising longitudinal support beam |
US11744603B2 (en) | 2021-03-24 | 2023-09-05 | Cilag Gmbh International | Multi-axis pivot joints for surgical instruments and methods for manufacturing same |
US11786239B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Surgical instrument articulation joint arrangements comprising multiple moving linkage features |
US11849945B2 (en) | 2021-03-24 | 2023-12-26 | Cilag Gmbh International | Rotary-driven surgical stapling assembly comprising eccentrically driven firing member |
US11786243B2 (en) | 2021-03-24 | 2023-10-17 | Cilag Gmbh International | Firing members having flexible portions for adapting to a load during a surgical firing stroke |
US11723662B2 (en) | 2021-05-28 | 2023-08-15 | Cilag Gmbh International | Stapling instrument comprising an articulation control display |
US11877745B2 (en) | 2021-10-18 | 2024-01-23 | Cilag Gmbh International | Surgical stapling assembly having longitudinally-repeating staple leg clusters |
US11957337B2 (en) | 2021-10-18 | 2024-04-16 | Cilag Gmbh International | Surgical stapling assembly with offset ramped drive surfaces |
US11980363B2 (en) | 2021-10-18 | 2024-05-14 | Cilag Gmbh International | Row-to-row staple array variations |
US11937816B2 (en) | 2021-10-28 | 2024-03-26 | Cilag Gmbh International | Electrical lead arrangements for surgical instruments |
Citations (69)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3812017A (en) * | 1972-07-26 | 1974-05-21 | Kennecott Copper Corp | Desulfurized char with phosphoric acid |
US3857932A (en) * | 1970-09-09 | 1974-12-31 | F Gould | Dry hydrophilic acrylate or methacrylate polymer prolonged release drug implants |
US4520821A (en) * | 1982-04-30 | 1985-06-04 | The Regents Of The University Of California | Growing of long-term biological tissue correction structures in vivo |
US4553272A (en) * | 1981-02-26 | 1985-11-19 | University Of Pittsburgh | Regeneration of living tissues by growth of isolated cells in porous implant and product thereof |
US4609551A (en) * | 1984-03-20 | 1986-09-02 | Arnold Caplan | Process of and material for stimulating growth of cartilage and bony tissue at anatomical sites |
US4801299A (en) * | 1983-06-10 | 1989-01-31 | University Patents, Inc. | Body implants of extracellular matrix and means and methods of making and using such implants |
US4902508A (en) * | 1988-07-11 | 1990-02-20 | Purdue Research Foundation | Tissue graft composition |
US5041138A (en) * | 1986-11-20 | 1991-08-20 | Massachusetts Institute Of Technology | Neomorphogenesis of cartilage in vivo from cell culture |
US5053050A (en) * | 1988-04-29 | 1991-10-01 | Samuel Itay | Compositions for repair of cartilage and bone |
US5061281A (en) * | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US5326357A (en) * | 1992-03-18 | 1994-07-05 | Mount Sinai Hospital Corporation | Reconstituted cartridge tissue |
US5425766A (en) * | 1987-03-09 | 1995-06-20 | Astra Tech Aktiebolag | Resorbable prosthesis |
US5443950A (en) * | 1986-04-18 | 1995-08-22 | Advanced Tissue Sciences, Inc. | Three-dimensional cell and tissue culture system |
US5445833A (en) * | 1991-09-24 | 1995-08-29 | Purdue Research Foundation | Tendon or ligament graft for promoting autogenous tissue growth |
US5480827A (en) * | 1991-07-19 | 1996-01-02 | Inoteb | Use of porous polycrystalline aragonite as a support material for in vitro culture of cells |
US5514181A (en) * | 1993-09-29 | 1996-05-07 | Johnson & Johnson Medical, Inc. | Absorbable structures for ligament and tendon repair |
US5577517A (en) * | 1990-06-28 | 1996-11-26 | Bonutti; Peter M. | Method of grafting human tissue particles |
US5681353A (en) * | 1987-07-20 | 1997-10-28 | Regen Biologics, Inc. | Meniscal augmentation device |
US5709854A (en) * | 1993-04-30 | 1998-01-20 | Massachusetts Institute Of Technology | Tissue formation by injecting a cell-polymeric solution that gels in vivo |
US5720969A (en) * | 1993-04-27 | 1998-02-24 | Cytotherapeutics, Inc. | Membrane formed by an acrylonitrile-based polymer |
US5736372A (en) * | 1986-11-20 | 1998-04-07 | Massachusetts Institute Of Technology | Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure |
US5755791A (en) * | 1996-04-05 | 1998-05-26 | Purdue Research Foundation | Perforated submucosal tissue graft constructs |
US5759190A (en) * | 1996-08-30 | 1998-06-02 | Vts Holdings Limited | Method and kit for autologous transplantation |
US5830493A (en) * | 1994-09-30 | 1998-11-03 | Yamanouchi Pharmaceutical Co., Ltd. | Bone-forming graft |
US5837235A (en) * | 1994-07-08 | 1998-11-17 | Sulzer Medizinaltechnik Ag | Process for regenerating bone and cartilage |
US5902741A (en) * | 1986-04-18 | 1999-05-11 | Advanced Tissue Sciences, Inc. | Three-dimensional cartilage cultures |
US5904716A (en) * | 1995-04-26 | 1999-05-18 | Gendler; El | Method for reconstituting cartilage tissue using demineralized bone and product thereof |
US5914121A (en) * | 1997-02-12 | 1999-06-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Formation of human bone in vivo using ceramic powder and human marrow stromal fibroblasts |
US5964805A (en) * | 1997-02-12 | 1999-10-12 | Stone; Kevin R. | Method and paste for articular cartilage transplantation |
US5980889A (en) * | 1993-08-10 | 1999-11-09 | Gore Hybrid Technologies, Inc. | Cell encapsulating device containing a cell displacing core for maintaining cell viability |
US5990194A (en) * | 1988-10-03 | 1999-11-23 | Atrix Laboratories, Inc. | Biodegradable in-situ forming implants and methods of producing the same |
US5989269A (en) * | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
US6027742A (en) * | 1995-05-19 | 2000-02-22 | Etex Corporation | Bioresorbable ceramic composites |
US6080576A (en) * | 1998-03-27 | 2000-06-27 | Lexicon Genetics Incorporated | Vectors for gene trapping and gene activation |
US6096532A (en) * | 1995-06-07 | 2000-08-01 | Aastrom Biosciences, Inc. | Processor apparatus for use in a system for maintaining and growing biological cells |
US6103255A (en) * | 1999-04-16 | 2000-08-15 | Rutgers, The State University | Porous polymer scaffolds for tissue engineering |
US6110209A (en) * | 1997-08-07 | 2000-08-29 | Stone; Kevin R. | Method and paste for articular cartilage transplantation |
US6120514A (en) * | 1996-08-30 | 2000-09-19 | Vts Holdings, Llc | Method and kit for autologous transplantation |
US6121042A (en) * | 1995-04-27 | 2000-09-19 | Advanced Tissue Sciences, Inc. | Apparatus and method for simulating in vivo conditions while seeding and culturing three-dimensional tissue constructs |
US6123727A (en) * | 1995-05-01 | 2000-09-26 | Massachusetts Institute Of Technology | Tissue engineered tendons and ligaments |
US6132463A (en) * | 1995-05-19 | 2000-10-17 | Etex Corporation | Cell seeding of ceramic compositions |
US6140039A (en) * | 1986-04-18 | 2000-10-31 | Advanced Tissue Sciences, Inc. | Three-dimensional filamentous tissue having tendon or ligament function |
US6143293A (en) * | 1998-03-26 | 2000-11-07 | Carnegie Mellon | Assembled scaffolds for three dimensional cell culturing and tissue generation |
US6183737B1 (en) * | 1997-10-30 | 2001-02-06 | The General Hospital Corporation | Bonding of cartilage pieces using isolated chondrocytes and a biological gel |
US6187053B1 (en) * | 1996-11-16 | 2001-02-13 | Will Minuth | Process for producing a natural implant |
US6197061B1 (en) * | 1999-03-01 | 2001-03-06 | Koichi Masuda | In vitro production of transplantable cartilage tissue cohesive cartilage produced thereby, and method for the surgical repair of cartilage damage |
US6200606B1 (en) * | 1996-01-16 | 2001-03-13 | Depuy Orthopaedics, Inc. | Isolation of precursor cells from hematopoietic and nonhematopoietic tissues and their use in vivo bone and cartilage regeneration |
US6214045B1 (en) * | 1997-10-10 | 2001-04-10 | John D. Corbitt, Jr. | Bioabsorbable breast implant |
US6251673B1 (en) * | 1996-09-10 | 2001-06-26 | Mediphore-Biotechnologie Ag | Method for manufacturing an implant consisting of a carrier material containing medically active agents |
US20010016353A1 (en) * | 1999-06-14 | 2001-08-23 | Janas Victor F. | Relic process for producing resorbable ceramic scaffolds |
US6287340B1 (en) * | 1999-05-14 | 2001-09-11 | Trustees Of Tufts College | Bioengineered anterior cruciate ligament |
US6291240B1 (en) * | 1998-01-29 | 2001-09-18 | Advanced Tissue Sciences, Inc. | Cells or tissues with increased protein factors and methods of making and using same |
US20010023373A1 (en) * | 1996-04-05 | 2001-09-20 | Plouhar Pamela L. | Tissue graft construct for replacement of cartilaginous structures |
US20010039453A1 (en) * | 1997-08-13 | 2001-11-08 | Gresser Joseph D. | Resorbable interbody spinal fusion devices |
US6319712B1 (en) * | 1998-01-30 | 2001-11-20 | Deutsche Institute Fur Textil-Und Faserforschung Stuttgart | Biohybrid articular surface replacement |
US20010053839A1 (en) * | 2000-06-19 | 2001-12-20 | Koken Co. Ltd. | Biomedical material and process for making same |
US20020009805A1 (en) * | 1999-07-06 | 2002-01-24 | Ramot University Authority For Applied Research & Industrial Development Ltd. | Scaffold matrix and tissue maintaining systems |
US20020009806A1 (en) * | 1999-05-27 | 2002-01-24 | Hicks Wesley L. | In vitro cell culture device including cartilage and methods of using the same |
US6365149B2 (en) * | 1999-06-30 | 2002-04-02 | Ethicon, Inc. | Porous tissue scaffoldings for the repair or regeneration of tissue |
US20020099448A1 (en) * | 1996-08-23 | 2002-07-25 | Michael C. Hiles | Multi-formed collagenous biomaterial medical device |
US20020107570A1 (en) * | 2000-12-08 | 2002-08-08 | Sybert Daryl R. | Biocompatible osteogenic band for repair of spinal disorders |
US20020127265A1 (en) * | 2000-12-21 | 2002-09-12 | Bowman Steven M. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US20020133229A1 (en) * | 2000-03-24 | 2002-09-19 | Laurencin Cato T. | Ligament and tendon replacement constructs and methods for production and use thereof |
US6511958B1 (en) * | 1997-08-14 | 2003-01-28 | Sulzer Biologics, Inc. | Compositions for regeneration and repair of cartilage lesions |
US20030026787A1 (en) * | 1999-08-06 | 2003-02-06 | Fearnot Neal E. | Tubular graft construct |
US6541024B1 (en) * | 1996-04-19 | 2003-04-01 | Osiris Therapeutics, Inc. | Regeneration and augmentation of bone using mesenchymal stem cells |
US20030077311A1 (en) * | 1999-06-30 | 2003-04-24 | Vyakarnam Murty N. | Foam composite for the repair or regeneration of tissue |
US6599323B2 (en) * | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
US6605294B2 (en) * | 1998-08-14 | 2003-08-12 | Incept Llc | Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels |
Family Cites Families (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6005161A (en) | 1986-01-28 | 1999-12-21 | Thm Biomedical, Inc. | Method and device for reconstruction of articular cartilage |
US5904717A (en) | 1986-01-28 | 1999-05-18 | Thm Biomedical, Inc. | Method and device for reconstruction of articular cartilage |
US5147400A (en) | 1989-05-10 | 1992-09-15 | United States Surgical Corporation | Connective tissue prosthesis |
US5108989A (en) | 1990-04-04 | 1992-04-28 | Genentech, Inc. | Method of predisposing mammals to accelerated tissue repair |
US5206023A (en) | 1991-01-31 | 1993-04-27 | Robert F. Shaw | Method and compositions for the treatment and repair of defects or lesions in cartilage |
WO1995005083A1 (en) | 1993-08-13 | 1995-02-23 | Smith & Nephew Richards Inc | Microporous polymeric foams and microtextured surfaces |
US5455041A (en) | 1993-09-13 | 1995-10-03 | Research Foundation Of State University Of New York At Buffalo | Method for inducing periodontal tissue regeneration |
GB2281861B (en) | 1993-09-21 | 1997-08-20 | Johnson & Johnson Medical | Bioabsorbable wound implant materials containing microspheres |
US5723331A (en) | 1994-05-05 | 1998-03-03 | Genzyme Corporation | Methods and compositions for the repair of articular cartilage defects in mammals |
US5632745A (en) | 1995-02-07 | 1997-05-27 | R&D Biologicals, Inc. | Surgical implantation of cartilage repair unit |
US5769899A (en) | 1994-08-12 | 1998-06-23 | Matrix Biotechnologies, Inc. | Cartilage repair unit |
US5891558A (en) | 1994-11-22 | 1999-04-06 | Tissue Engineering, Inc. | Biopolymer foams for use in tissue repair and reconstruction |
GB9510624D0 (en) | 1995-05-25 | 1995-07-19 | Ellis Dev Ltd | Textile surgical implants |
FR2737663B1 (en) | 1995-08-07 | 1997-10-03 | Centre Nat Rech Scient | COMPOSITION FOR BIO-MATERIAL, METHOD OF PREPARATION |
US5842477A (en) | 1996-02-21 | 1998-12-01 | Advanced Tissue Sciences, Inc. | Method for repairing cartilage |
US6001352A (en) | 1997-03-31 | 1999-12-14 | Osteobiologics, Inc. | Resurfacing cartilage defects with chondrocytes proliferated without differentiation using platelet-derived growth factor |
US6080579A (en) | 1997-11-26 | 2000-06-27 | Charlotte-Mecklenburg Hospital Authority | Method for producing human intervertebral disc cells |
US6179872B1 (en) * | 1998-03-17 | 2001-01-30 | Tissue Engineering | Biopolymer matt for use in tissue repair and reconstruction |
-
2000
- 2000-12-21 US US09/747,488 patent/US6852330B2/en not_active Expired - Lifetime
Patent Citations (82)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3857932A (en) * | 1970-09-09 | 1974-12-31 | F Gould | Dry hydrophilic acrylate or methacrylate polymer prolonged release drug implants |
US3812017A (en) * | 1972-07-26 | 1974-05-21 | Kennecott Copper Corp | Desulfurized char with phosphoric acid |
US4553272A (en) * | 1981-02-26 | 1985-11-19 | University Of Pittsburgh | Regeneration of living tissues by growth of isolated cells in porous implant and product thereof |
US4520821A (en) * | 1982-04-30 | 1985-06-04 | The Regents Of The University Of California | Growing of long-term biological tissue correction structures in vivo |
US4801299A (en) * | 1983-06-10 | 1989-01-31 | University Patents, Inc. | Body implants of extracellular matrix and means and methods of making and using such implants |
US4609551A (en) * | 1984-03-20 | 1986-09-02 | Arnold Caplan | Process of and material for stimulating growth of cartilage and bony tissue at anatomical sites |
US5061281A (en) * | 1985-12-17 | 1991-10-29 | Allied-Signal Inc. | Bioresorbable polymers and implantation devices thereof |
US5443950A (en) * | 1986-04-18 | 1995-08-22 | Advanced Tissue Sciences, Inc. | Three-dimensional cell and tissue culture system |
US6140039A (en) * | 1986-04-18 | 2000-10-31 | Advanced Tissue Sciences, Inc. | Three-dimensional filamentous tissue having tendon or ligament function |
US5902741A (en) * | 1986-04-18 | 1999-05-11 | Advanced Tissue Sciences, Inc. | Three-dimensional cartilage cultures |
US5041138A (en) * | 1986-11-20 | 1991-08-20 | Massachusetts Institute Of Technology | Neomorphogenesis of cartilage in vivo from cell culture |
US5736372A (en) * | 1986-11-20 | 1998-04-07 | Massachusetts Institute Of Technology | Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure |
US5425766A (en) * | 1987-03-09 | 1995-06-20 | Astra Tech Aktiebolag | Resorbable prosthesis |
US5681353A (en) * | 1987-07-20 | 1997-10-28 | Regen Biologics, Inc. | Meniscal augmentation device |
US5053050A (en) * | 1988-04-29 | 1991-10-01 | Samuel Itay | Compositions for repair of cartilage and bone |
US4902508A (en) * | 1988-07-11 | 1990-02-20 | Purdue Research Foundation | Tissue graft composition |
US5990194A (en) * | 1988-10-03 | 1999-11-23 | Atrix Laboratories, Inc. | Biodegradable in-situ forming implants and methods of producing the same |
US20020091406A1 (en) * | 1990-06-28 | 2002-07-11 | Bonutti Peter M. | Apparatus and method for tissue removal |
US5577517A (en) * | 1990-06-28 | 1996-11-26 | Bonutti; Peter M. | Method of grafting human tissue particles |
US20020099401A1 (en) * | 1990-06-28 | 2002-07-25 | Bonutti Petel M. | Apparatus and method for tissue removal |
US20020091403A1 (en) * | 1990-06-28 | 2002-07-11 | Bonutti Peter M. | Cell harvesting method |
US20020082631A1 (en) * | 1990-06-28 | 2002-06-27 | Bonutti Peter M. | Apparatus and method for tissue removal |
US20020029055A1 (en) * | 1990-06-28 | 2002-03-07 | Bonutti Peter M. | Apparatus and method for tissue removal |
US5480827A (en) * | 1991-07-19 | 1996-01-02 | Inoteb | Use of porous polycrystalline aragonite as a support material for in vitro culture of cells |
US5445833A (en) * | 1991-09-24 | 1995-08-29 | Purdue Research Foundation | Tendon or ligament graft for promoting autogenous tissue growth |
US5326357A (en) * | 1992-03-18 | 1994-07-05 | Mount Sinai Hospital Corporation | Reconstituted cartridge tissue |
US5720969A (en) * | 1993-04-27 | 1998-02-24 | Cytotherapeutics, Inc. | Membrane formed by an acrylonitrile-based polymer |
US6180007B1 (en) * | 1993-04-27 | 2001-01-30 | Neurotech, Sa | Membrane formed by an acrylonitrile-based polymer |
US5709854A (en) * | 1993-04-30 | 1998-01-20 | Massachusetts Institute Of Technology | Tissue formation by injecting a cell-polymeric solution that gels in vivo |
US20010053353A1 (en) * | 1993-04-30 | 2001-12-20 | Griffith Linda G | Injectable polysaccharide-cell compositions |
US5980889A (en) * | 1993-08-10 | 1999-11-09 | Gore Hybrid Technologies, Inc. | Cell encapsulating device containing a cell displacing core for maintaining cell viability |
US5514181A (en) * | 1993-09-29 | 1996-05-07 | Johnson & Johnson Medical, Inc. | Absorbable structures for ligament and tendon repair |
US5837235A (en) * | 1994-07-08 | 1998-11-17 | Sulzer Medizinaltechnik Ag | Process for regenerating bone and cartilage |
US5830493A (en) * | 1994-09-30 | 1998-11-03 | Yamanouchi Pharmaceutical Co., Ltd. | Bone-forming graft |
US5904716A (en) * | 1995-04-26 | 1999-05-18 | Gendler; El | Method for reconstituting cartilage tissue using demineralized bone and product thereof |
US6121042A (en) * | 1995-04-27 | 2000-09-19 | Advanced Tissue Sciences, Inc. | Apparatus and method for simulating in vivo conditions while seeding and culturing three-dimensional tissue constructs |
US6123727A (en) * | 1995-05-01 | 2000-09-26 | Massachusetts Institute Of Technology | Tissue engineered tendons and ligaments |
US6139578A (en) * | 1995-05-19 | 2000-10-31 | Etex Corporation | Preparation of cell seeded ceramic compositions |
US6331312B1 (en) * | 1995-05-19 | 2001-12-18 | Etex Corporation | Bioresorbable ceramic composites |
US6277151B1 (en) * | 1995-05-19 | 2001-08-21 | Etex Corporation | Cartilage growth from cell seeded ceramic compositions |
US6132463A (en) * | 1995-05-19 | 2000-10-17 | Etex Corporation | Cell seeding of ceramic compositions |
US6027742A (en) * | 1995-05-19 | 2000-02-22 | Etex Corporation | Bioresorbable ceramic composites |
US6096532A (en) * | 1995-06-07 | 2000-08-01 | Aastrom Biosciences, Inc. | Processor apparatus for use in a system for maintaining and growing biological cells |
US6200606B1 (en) * | 1996-01-16 | 2001-03-13 | Depuy Orthopaedics, Inc. | Isolation of precursor cells from hematopoietic and nonhematopoietic tissues and their use in vivo bone and cartilage regeneration |
US5968096A (en) * | 1996-04-05 | 1999-10-19 | Purdue Research Foundation | Method of repairing perforated submucosal tissue graft constructs |
US20010023373A1 (en) * | 1996-04-05 | 2001-09-20 | Plouhar Pamela L. | Tissue graft construct for replacement of cartilaginous structures |
US5755791A (en) * | 1996-04-05 | 1998-05-26 | Purdue Research Foundation | Perforated submucosal tissue graft constructs |
US6541024B1 (en) * | 1996-04-19 | 2003-04-01 | Osiris Therapeutics, Inc. | Regeneration and augmentation of bone using mesenchymal stem cells |
US20020099448A1 (en) * | 1996-08-23 | 2002-07-25 | Michael C. Hiles | Multi-formed collagenous biomaterial medical device |
US6283980B1 (en) * | 1996-08-30 | 2001-09-04 | Verigen Transplantation Services Internt'l | Method, instruments, and kit for autologous transplantation |
US6120514A (en) * | 1996-08-30 | 2000-09-19 | Vts Holdings, Llc | Method and kit for autologous transplantation |
US5759190A (en) * | 1996-08-30 | 1998-06-02 | Vts Holdings Limited | Method and kit for autologous transplantation |
US6379367B1 (en) * | 1996-08-30 | 2002-04-30 | Verigen Transplantation Service International (Vtsi) Ag | Method instruments and kit for autologous transplantation |
US5989269A (en) * | 1996-08-30 | 1999-11-23 | Vts Holdings L.L.C. | Method, instruments and kit for autologous transplantation |
US6251673B1 (en) * | 1996-09-10 | 2001-06-26 | Mediphore-Biotechnologie Ag | Method for manufacturing an implant consisting of a carrier material containing medically active agents |
US6187053B1 (en) * | 1996-11-16 | 2001-02-13 | Will Minuth | Process for producing a natural implant |
US5914121A (en) * | 1997-02-12 | 1999-06-22 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Formation of human bone in vivo using ceramic powder and human marrow stromal fibroblasts |
US5964805A (en) * | 1997-02-12 | 1999-10-12 | Stone; Kevin R. | Method and paste for articular cartilage transplantation |
US6110209A (en) * | 1997-08-07 | 2000-08-29 | Stone; Kevin R. | Method and paste for articular cartilage transplantation |
US20010039453A1 (en) * | 1997-08-13 | 2001-11-08 | Gresser Joseph D. | Resorbable interbody spinal fusion devices |
US6511958B1 (en) * | 1997-08-14 | 2003-01-28 | Sulzer Biologics, Inc. | Compositions for regeneration and repair of cartilage lesions |
US6214045B1 (en) * | 1997-10-10 | 2001-04-10 | John D. Corbitt, Jr. | Bioabsorbable breast implant |
US6183737B1 (en) * | 1997-10-30 | 2001-02-06 | The General Hospital Corporation | Bonding of cartilage pieces using isolated chondrocytes and a biological gel |
US6291240B1 (en) * | 1998-01-29 | 2001-09-18 | Advanced Tissue Sciences, Inc. | Cells or tissues with increased protein factors and methods of making and using same |
US6319712B1 (en) * | 1998-01-30 | 2001-11-20 | Deutsche Institute Fur Textil-Und Faserforschung Stuttgart | Biohybrid articular surface replacement |
US6143293A (en) * | 1998-03-26 | 2000-11-07 | Carnegie Mellon | Assembled scaffolds for three dimensional cell culturing and tissue generation |
US6080576A (en) * | 1998-03-27 | 2000-06-27 | Lexicon Genetics Incorporated | Vectors for gene trapping and gene activation |
US6605294B2 (en) * | 1998-08-14 | 2003-08-12 | Incept Llc | Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels |
US6197061B1 (en) * | 1999-03-01 | 2001-03-06 | Koichi Masuda | In vitro production of transplantable cartilage tissue cohesive cartilage produced thereby, and method for the surgical repair of cartilage damage |
US6103255A (en) * | 1999-04-16 | 2000-08-15 | Rutgers, The State University | Porous polymer scaffolds for tissue engineering |
US6287340B1 (en) * | 1999-05-14 | 2001-09-11 | Trustees Of Tufts College | Bioengineered anterior cruciate ligament |
US20020009806A1 (en) * | 1999-05-27 | 2002-01-24 | Hicks Wesley L. | In vitro cell culture device including cartilage and methods of using the same |
US20010016353A1 (en) * | 1999-06-14 | 2001-08-23 | Janas Victor F. | Relic process for producing resorbable ceramic scaffolds |
US6365149B2 (en) * | 1999-06-30 | 2002-04-02 | Ethicon, Inc. | Porous tissue scaffoldings for the repair or regeneration of tissue |
US20030077311A1 (en) * | 1999-06-30 | 2003-04-24 | Vyakarnam Murty N. | Foam composite for the repair or regeneration of tissue |
US20020009805A1 (en) * | 1999-07-06 | 2002-01-24 | Ramot University Authority For Applied Research & Industrial Development Ltd. | Scaffold matrix and tissue maintaining systems |
US20030026787A1 (en) * | 1999-08-06 | 2003-02-06 | Fearnot Neal E. | Tubular graft construct |
US20020133229A1 (en) * | 2000-03-24 | 2002-09-19 | Laurencin Cato T. | Ligament and tendon replacement constructs and methods for production and use thereof |
US20010053839A1 (en) * | 2000-06-19 | 2001-12-20 | Koken Co. Ltd. | Biomedical material and process for making same |
US20020107570A1 (en) * | 2000-12-08 | 2002-08-08 | Sybert Daryl R. | Biocompatible osteogenic band for repair of spinal disorders |
US20020127265A1 (en) * | 2000-12-21 | 2002-09-12 | Bowman Steven M. | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US6599323B2 (en) * | 2000-12-21 | 2003-07-29 | Ethicon, Inc. | Reinforced tissue implants and methods of manufacture and use |
Cited By (182)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8449561B2 (en) | 1999-07-23 | 2013-05-28 | Depuy Mitek, Llc | Graft fixation device combination |
US8016867B2 (en) | 1999-07-23 | 2011-09-13 | Depuy Mitek, Inc. | Graft fixation device and method |
US8920304B2 (en) | 2000-07-05 | 2014-12-30 | Coloplast A/S | Method and device for treating urinary incontinence |
US8469875B2 (en) | 2000-07-05 | 2013-06-25 | Coloplast A/S | Method and device for treating urinary incontinence |
US10278800B2 (en) | 2000-07-05 | 2019-05-07 | Coloplast A/S | Method and device for treating urinary incontinence |
US8182413B2 (en) | 2000-10-12 | 2012-05-22 | Coloplast A/S | Method for fibrous anchoring of a pelvic support |
US8888678B2 (en) | 2000-10-12 | 2014-11-18 | Coloplast A/S | Pelvic implant with suspending system |
US8668635B2 (en) | 2000-10-12 | 2014-03-11 | Coloplast A/S | Pelvic implant with suspending system |
US8162818B2 (en) | 2000-10-12 | 2012-04-24 | Coloplast A/S | Adjustable surgical implant for pelvic anatomy |
US8821369B2 (en) | 2000-10-12 | 2014-09-02 | Colorplast A/S | Method for soft tissue anchoring with introducer |
US8128554B2 (en) | 2000-10-12 | 2012-03-06 | Coloplast A/S | System for introducing a pelvic implant |
US8123673B2 (en) | 2000-10-12 | 2012-02-28 | Coloplast A/S | Adjustable surgical implant for treating urinary incontinence |
US8118727B2 (en) | 2000-10-12 | 2012-02-21 | Coloplast A/S | Method for supporting pelvic anatomy |
US8574148B2 (en) | 2000-10-12 | 2013-11-05 | Coloplast A/S | System for introducing soft tissue anchors |
US8118728B2 (en) | 2000-10-12 | 2012-02-21 | Coloplast A/S | Method for implanting an adjustable surgical implant for treating urinary incontinence |
US8047983B2 (en) | 2000-10-12 | 2011-11-01 | Coloplast A/S | Surgical system for supporting pelvic anatomy |
US8182412B2 (en) | 2000-10-12 | 2012-05-22 | Coloplast A/S | Pelvic implant with fibrous anchor |
US8007430B2 (en) | 2000-10-12 | 2011-08-30 | Coloplast A/S | Apparatus and method for treating female urinary incontinence |
US9113992B2 (en) | 2000-10-12 | 2015-08-25 | Coloplast A/S | Apparatus and method for treating urinary incontinence |
US8801596B2 (en) | 2000-10-12 | 2014-08-12 | Coloplast A/S | Sling with support and suspending members formed from same polymer |
US9089394B2 (en) | 2000-10-12 | 2015-07-28 | Coloplast A/S | Pelvic implant with suspending system |
US9089396B2 (en) | 2000-10-12 | 2015-07-28 | Coloplast A/S | Urinary incontinence treatment and devices |
US9968430B2 (en) | 2000-10-12 | 2018-05-15 | Coloplast A/S | Surgical device implantable to treat female urinary incontinence |
US9918817B2 (en) | 2000-10-12 | 2018-03-20 | Coloplast A/S | Method of post-operatively adjusting a urethral support in treating urinary incontinence of a woman |
US8932202B2 (en) | 2000-10-12 | 2015-01-13 | Coloplast A/S | Incontinence implant with soft tissue anchors and length not allowing abdominal wall penetration |
US8852075B2 (en) | 2000-10-12 | 2014-10-07 | Coloplast A/S | Pelvic implant systems and methods with expandable anchors |
US8512223B2 (en) | 2000-10-12 | 2013-08-20 | Coloplast A/S | Pelvic implant with selective locking anchor |
US8821370B2 (en) | 2000-10-12 | 2014-09-02 | Coloplast A/S | Device, system and methods for introducing soft tissue anchors |
US8920308B2 (en) | 2000-10-12 | 2014-12-30 | Coloplast A/S | Surgical implant with anchor introducer channel |
US10449025B2 (en) | 2000-10-12 | 2019-10-22 | Coloplast A/S | Surgical device implantable to treat female urinary incontinence |
US8911347B2 (en) | 2000-10-12 | 2014-12-16 | Coloplast A/S | System and method for treating urinary incontinence |
US8273011B2 (en) | 2000-10-12 | 2012-09-25 | Coloplast A/S | Adjustable surgical implant and method for treating urinary incontinence |
US8449450B2 (en) | 2000-10-12 | 2013-05-28 | Coloplast A/S | Pass through introducer and sling |
US8469877B2 (en) | 2000-10-12 | 2013-06-25 | Coloplast A/S | System for introducing a pelvic implant |
US8454492B2 (en) | 2000-10-12 | 2013-06-04 | Coloplast A/S | Absorbable anchor and method for mounting mesh to tissue |
US8167785B2 (en) | 2000-10-12 | 2012-05-01 | Coloplast A/S | Urethral support system |
US10076394B2 (en) | 2000-10-12 | 2018-09-18 | Coloplast A/S | Method of treating urinary incontinence |
US8691259B2 (en) | 2000-12-21 | 2014-04-08 | Depuy Mitek, Llc | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration |
US9943390B2 (en) | 2001-03-30 | 2018-04-17 | Coloplast A/S | Method of treating pelvic organ prolapse in a female patient by accessing a prolapsed organ trans-vaginally through a vagina |
US10682213B2 (en) | 2001-03-30 | 2020-06-16 | Coloplast A/S | Surgical implant consisting of non-absorbable material |
US20050010306A1 (en) * | 2001-11-14 | 2005-01-13 | Jorg Priewe | Areal implant |
US7615065B2 (en) * | 2001-11-14 | 2009-11-10 | Ethicon Inc. | Areal implant |
US20030220700A1 (en) * | 2002-05-22 | 2003-11-27 | Hammer Joseph J. | Attachment of absorbable tissue scaffolds ot fixation devices |
US8187326B2 (en) * | 2002-05-22 | 2012-05-29 | Advanced Technologies And Regenerative Medicine, Llc. | Attachment of absorbable tissue scaffolds to fixation devices |
US6989034B2 (en) * | 2002-05-31 | 2006-01-24 | Ethicon, Inc. | Attachment of absorbable tissue scaffolds to fixation devices |
US20030225459A1 (en) * | 2002-05-31 | 2003-12-04 | Hammer Joseph J. | Attachment of absorbable tissue scaffolds to fixation devices |
US9005222B2 (en) | 2002-08-02 | 2015-04-14 | Coloplast A/S | Self-anchoring sling and introducer system |
US9872750B2 (en) | 2002-08-02 | 2018-01-23 | Coloplast A/S | Self-anchoring sling and introducer system |
US9532861B2 (en) | 2002-08-02 | 2017-01-03 | Coloplast A/S | Self-anchoring sling and introducer system |
US9532862B2 (en) | 2002-08-02 | 2017-01-03 | Coloplast A/S | Self-anchoring sling and introducer system |
US6958078B2 (en) * | 2002-08-19 | 2005-10-25 | The University Of Toledo | Bioartificial intervertebral disc |
US20040034427A1 (en) * | 2002-08-19 | 2004-02-19 | Goel Vijay K. | Bioartificial intervertebral disc |
US8637066B2 (en) | 2002-10-18 | 2014-01-28 | Depuy Mitek, Llc | Biocompatible scaffold for ligament or tendon repair |
US9511171B2 (en) | 2002-10-18 | 2016-12-06 | Depuy Mitek, Llc | Biocompatible scaffolds with tissue fragments |
US7824701B2 (en) | 2002-10-18 | 2010-11-02 | Ethicon, Inc. | Biocompatible scaffold for ligament or tendon repair |
US10603408B2 (en) | 2002-10-18 | 2020-03-31 | DePuy Synthes Products, Inc. | Biocompatible scaffolds with tissue fragments |
US20060229721A1 (en) * | 2003-01-17 | 2006-10-12 | Ku David N | Solid implant |
US8895045B2 (en) | 2003-03-07 | 2014-11-25 | Depuy Mitek, Llc | Method of preparation of bioabsorbable porous reinforced tissue implants and implants thereof |
US9186489B2 (en) | 2003-03-27 | 2015-11-17 | Coloplast A/S | Implantable delivery device system for delivery of a medicament to a bladder |
US9345867B2 (en) | 2003-03-27 | 2016-05-24 | Coloplast A/S | Device implantable in tissue of a prostate gland or a bladder |
US9555168B2 (en) | 2003-03-27 | 2017-01-31 | Coloplast A/S | System for delivery of medication in treatment of disorders of the pelvis |
US8709471B2 (en) | 2003-03-27 | 2014-04-29 | Coloplast A/S | Medicament delivery device and a method of medicament delivery |
US8562542B2 (en) | 2003-03-28 | 2013-10-22 | Depuy Mitek, Llc | Tissue collection device and methods |
US20040249473A1 (en) * | 2003-03-28 | 2004-12-09 | Analytic Biosurgical Solutions- Abiss | Implant for treating rectocele and a device for putting said implant into place |
US20040249397A1 (en) * | 2003-03-28 | 2004-12-09 | Analytic Biosurgical Solutions- Abiss | Method and implant for curing cystocele |
EP1466632A1 (en) * | 2003-04-02 | 2004-10-13 | Lifescan, Inc. | Implantable pouch seeded with insulin-producing cells to treat diabetes |
CN100404074C (en) * | 2003-04-02 | 2008-07-23 | 生命扫描有限公司 | Implantable pouch seeded with insulin-producing cells to treat diabetes |
US7803395B2 (en) | 2003-05-15 | 2010-09-28 | Biomerix Corporation | Reticulated elastomeric matrices, their manufacture and use in implantable devices |
US9211362B2 (en) | 2003-06-30 | 2015-12-15 | Depuy Mitek, Llc | Scaffold for connective tissue repair |
US8226715B2 (en) | 2003-06-30 | 2012-07-24 | Depuy Mitek, Inc. | Scaffold for connective tissue repair |
US10583220B2 (en) | 2003-08-11 | 2020-03-10 | DePuy Synthes Products, Inc. | Method and apparatus for resurfacing an articular surface |
US7611473B2 (en) | 2003-09-11 | 2009-11-03 | Ethicon, Inc. | Tissue extraction and maceration device |
US8585610B2 (en) | 2003-09-11 | 2013-11-19 | Depuy Mitek, Llc | Tissue extraction and maceration device |
US8034003B2 (en) | 2003-09-11 | 2011-10-11 | Depuy Mitek, Inc. | Tissue extraction and collection device |
US8870788B2 (en) | 2003-09-11 | 2014-10-28 | Depuy Mitek, Llc | Tissue extraction and collection device |
US7998086B2 (en) | 2003-09-11 | 2011-08-16 | Depuy Mitek, Inc. | Tissue extraction and maceration device |
US8137702B2 (en) | 2003-11-26 | 2012-03-20 | Depuy Mitek, Inc. | Conformable tissue repair implant capable of injection delivery |
US8496970B2 (en) | 2003-11-26 | 2013-07-30 | Depuy Mitek, Llc | Conformable tissue repair implant capable of injection delivery |
US20080071385A1 (en) * | 2003-11-26 | 2008-03-20 | Depuy Mitek, Inc. | Conformable tissue repair implant capable of injection delivery |
US7875296B2 (en) | 2003-11-26 | 2011-01-25 | Depuy Mitek, Inc. | Conformable tissue repair implant capable of injection delivery |
US20110177134A1 (en) * | 2003-12-05 | 2011-07-21 | Depuy Mitek, Inc. | Viable Tissue Repair Implants and Methods of Use |
US7901461B2 (en) | 2003-12-05 | 2011-03-08 | Ethicon, Inc. | Viable tissue repair implants and methods of use |
US8641775B2 (en) * | 2003-12-05 | 2014-02-04 | Depuy Mitek, Llc | Viable tissue repair implants and methods of use |
US7666230B2 (en) | 2003-12-08 | 2010-02-23 | Depuy Products, Inc. | Implant device for cartilage regeneration in load bearing articulation regions |
EP1541095A2 (en) | 2003-12-08 | 2005-06-15 | Depuy Products, Inc. | Implant device for cartilage regeneration in load bearing articulation regions |
US20050125073A1 (en) * | 2003-12-08 | 2005-06-09 | Orban Janine M. | Implant device for cartilage regeneration in load bearing articulation regions |
US7763077B2 (en) | 2003-12-24 | 2010-07-27 | Biomerix Corporation | Repair of spinal annular defects and annulo-nucleoplasty regeneration |
US11779680B2 (en) | 2004-01-09 | 2023-10-10 | Rti Surgical, Inc. | Connective-tissue-based or dermal-tissue-based grafts/implants |
US10814034B2 (en) | 2004-01-09 | 2020-10-27 | Rti Surgical, Inc. | Connective-tissue-based or dermal-tissue-based grafts/implants |
US10022472B2 (en) | 2004-01-09 | 2018-07-17 | Rti Surgical, Inc. | Connective-tissue-based or dermal-tissue-based grafts/implants |
US8747467B2 (en) | 2004-01-09 | 2014-06-10 | Rti Surgical, Inc. | Muscle-based grafts/implants |
US7001430B2 (en) | 2004-01-09 | 2006-02-21 | Regeneration Technologies, Inc. | Matrix composition for human grafts/implants |
WO2005070328A1 (en) * | 2004-01-09 | 2005-08-04 | Regeneration Technologies, Inc. | Muscle-based grafts/implants |
US20050152880A1 (en) * | 2004-01-09 | 2005-07-14 | Regeneration Technologies, Inc. | Matrix composition for human grafts/implants |
US20050152881A1 (en) * | 2004-01-09 | 2005-07-14 | Regeneration Technologies, Inc. | Muscle-based grafts/implants |
US7131994B2 (en) | 2004-01-09 | 2006-11-07 | Regeneration Technologies, Inc. | Muscle-based grafts/implants |
US9398948B2 (en) | 2004-01-09 | 2016-07-26 | Rti Surgical, Inc. | Connective-tissue-based or dermal-tissue-based grafts/implants |
US20110091516A1 (en) * | 2004-01-09 | 2011-04-21 | Regeneration Technologies, Inc. | Muscle-based grafts/implants |
US11395865B2 (en) | 2004-02-09 | 2022-07-26 | DePuy Synthes Products, Inc. | Scaffolds with viable tissue |
US7767221B2 (en) | 2004-03-05 | 2010-08-03 | The Trustees Of Columbia University In The City Of New York | Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone |
US8802122B2 (en) | 2004-03-05 | 2014-08-12 | The Trustees Of Columbia University In The City Of New York | Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue of bone |
US9427495B2 (en) | 2004-03-05 | 2016-08-30 | The Trustees Of Columbia University In The City Of New York | Multi-phased, biodegradable and oesteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone |
US20060036331A1 (en) * | 2004-03-05 | 2006-02-16 | Lu Helen H | Polymer-ceramic-hydrogel composite scaffold for osteochondral repair |
US20060067969A1 (en) * | 2004-03-05 | 2006-03-30 | Lu Helen H | Multi-phased, biodegradable and osteointegrative composite scaffold for biological fixation of musculoskeletal soft tissue to bone |
US8137686B2 (en) | 2004-04-20 | 2012-03-20 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US8221780B2 (en) | 2004-04-20 | 2012-07-17 | Depuy Mitek, Inc. | Nonwoven tissue scaffold |
US7407511B2 (en) * | 2004-05-13 | 2008-08-05 | Wright Medical Technology Inc | Methods and materials for connective tissue repair |
US20050255140A1 (en) * | 2004-05-13 | 2005-11-17 | Hagan Cary P | Methods and materials for connective tissue repair |
US7975698B2 (en) | 2004-05-21 | 2011-07-12 | Coloplast A/S | Implant for treatment of vaginal and/or uterine prolapse |
US9060838B2 (en) | 2004-05-21 | 2015-06-23 | Coloplast A/S | Tissue supported implantable device |
US10064714B2 (en) | 2004-05-21 | 2018-09-04 | Coloplast A/S | Implantable device configured to treat pelvic organ prolapse |
US8215310B2 (en) | 2004-05-21 | 2012-07-10 | Coloplast A/S | Implant for treatment of vaginal and/or uterine prolapse |
US20050288692A1 (en) * | 2004-06-15 | 2005-12-29 | Jean-Marc Beraud | Parietal hook |
US7758615B2 (en) | 2004-06-15 | 2010-07-20 | Colopast A/S | Parietal hook |
US20080051809A1 (en) * | 2004-08-09 | 2008-02-28 | Verde Bvba | Implant for Treating Rotator Cuff Injuiries |
US20080220521A1 (en) * | 2004-10-25 | 2008-09-11 | Gc Corporation | Sheet for guiding regeneration of mesenchymal tissue and production method thereof |
US8771294B2 (en) | 2004-11-26 | 2014-07-08 | Biomerix Corporation | Aneurysm treatment devices and methods |
WO2006116210A2 (en) * | 2005-04-25 | 2006-11-02 | Bernstein Eric F | Dermal fillers for biomedical applications in mammals and methods of using the same |
WO2006116210A3 (en) * | 2005-04-25 | 2008-03-20 | Eric F Bernstein | Dermal fillers for biomedical applications in mammals and methods of using the same |
EP1743663A2 (en) * | 2005-06-29 | 2007-01-17 | Lifescan, Inc. | Multi-compartment delivery system |
EP1743663A3 (en) * | 2005-06-29 | 2007-09-19 | Lifescan, Inc. | Multi-compartment delivery system |
US7900484B2 (en) | 2006-10-19 | 2011-03-08 | C.R. Bard, Inc. | Prosthetic repair fabric |
US20100047309A1 (en) * | 2006-12-06 | 2010-02-25 | Lu Helen H | Graft collar and scaffold apparatuses for musculoskeletal tissue engineering and related methods |
US20080188936A1 (en) * | 2007-02-02 | 2008-08-07 | Tornier, Inc. | System and method for repairing tendons and ligaments |
US10265155B2 (en) * | 2007-02-12 | 2019-04-23 | The Trustees Of Columbia University In The City Of New York | Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement |
US20100292791A1 (en) * | 2007-02-12 | 2010-11-18 | Lu Helen H | Fully synthetic implantable multi-phased scaffold |
US20150100121A1 (en) * | 2007-02-12 | 2015-04-09 | The Trustees Of Columbia University In The City Of New York | Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement |
US8864843B2 (en) * | 2007-02-12 | 2014-10-21 | The Trustees Of Columbia University In The City Of New York | Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement |
US8753391B2 (en) * | 2007-02-12 | 2014-06-17 | The Trustees Of Columbia University In The City Of New York | Fully synthetic implantable multi-phased scaffold |
US20110066242A1 (en) * | 2007-02-12 | 2011-03-17 | The Trustees Of Columbia University In The City Of New York | Biomimmetic nanofiber scaffold for soft tissue and soft tissue-to-bone repair, augmentation and replacement |
US10639138B2 (en) | 2008-02-28 | 2020-05-05 | Coloplast A/S | Method for providing support to a urethra in treating urinary incontinence |
US11844528B2 (en) | 2008-04-21 | 2023-12-19 | Covidien Lp | Multiple layer filamentary devices for treatment of vascular defects |
US11707371B2 (en) | 2008-05-13 | 2023-07-25 | Covidien Lp | Braid implant delivery systems |
US20220338974A1 (en) * | 2009-01-08 | 2022-10-27 | Rotation Medical, Inc. | Implantable tendon protection systems and related kits and methods |
US12016769B2 (en) * | 2009-01-08 | 2024-06-25 | Rotation Medical, Inc. | Implantable tendon protection systems and related kits and methods |
US20100318108A1 (en) * | 2009-02-02 | 2010-12-16 | Biomerix Corporation | Composite mesh devices and methods for soft tissue repair |
US10821005B2 (en) | 2009-03-27 | 2020-11-03 | DePuy Synthes Products, Inc. | Methods and devices for delivering and affixing tissue scaffolds |
US9421082B2 (en) | 2009-03-27 | 2016-08-23 | Depuy Mitek, Llc | Methods and devices for preparing and implanting tissue scaffolds |
US8308814B2 (en) | 2009-03-27 | 2012-11-13 | Depuy Mitek, Inc. | Methods and devices for preparing and implanting tissue scaffolds |
US11589995B2 (en) | 2009-03-27 | 2023-02-28 | DePuy Synthes Products, Inc. | Methods and devices for preparing and implanting tissue scaffolds |
US10449052B2 (en) | 2009-03-27 | 2019-10-22 | Depuy Synthes Products, Inc | Methods and devices for preparing and implanting tissue scaffolds |
US8241298B2 (en) | 2009-03-27 | 2012-08-14 | Depuy Mitek, Inc. | Methods and devices for delivering and affixing tissue scaffolds |
US11554028B2 (en) | 2009-03-27 | 2023-01-17 | DePuy Synthes Products, Inc. | Methods and devices for delivering and affixing tissue scaffolds |
US9848999B2 (en) | 2009-03-27 | 2017-12-26 | Depuy Mitek, Llc | Methods and devices for delivering and affixing tissue scaffolds |
US20100249758A1 (en) * | 2009-03-27 | 2010-09-30 | Depuy Mitek, Inc. | Methods and devices for preparing and implanting tissue scaffolds |
US8469980B2 (en) | 2009-03-27 | 2013-06-25 | Depuy Mitek, Llc | Methods and devices for preparing and implanting tissue scaffolds |
US9149369B2 (en) | 2009-03-27 | 2015-10-06 | Depuy Mitek, Llc | Methods and devices for delivering and affixing tissue scaffolds |
US9289299B2 (en) * | 2010-02-18 | 2016-03-22 | Biomet Manufacturing, Llc | Method and apparatus for augumenting bone defects |
US20130211536A1 (en) * | 2010-02-18 | 2013-08-15 | Biomet Manufacturing Corporation | Method And Apparatus For Augumenting Bone Defects |
US11690628B2 (en) | 2012-11-13 | 2023-07-04 | Covidien Lp | Occlusive devices |
US20140135811A1 (en) * | 2012-11-13 | 2014-05-15 | Covidien Lp | Occlusive devices |
US10327781B2 (en) | 2012-11-13 | 2019-06-25 | Covidien Lp | Occlusive devices |
US11786253B2 (en) | 2012-11-13 | 2023-10-17 | Covidien Lp | Occlusive devices |
US11110199B2 (en) | 2013-04-12 | 2021-09-07 | The Trustees Of Columbia University In The City Of New York | Methods for host cell homing and dental pulp regeneration |
EP3750507A1 (en) | 2014-02-17 | 2020-12-16 | Establishment Labs S.A. | Textured surfaces for breast implants |
US10595979B2 (en) | 2014-02-17 | 2020-03-24 | Establishment Labs S.A. | Textured surfaces for breast implants |
US10912636B2 (en) | 2014-02-17 | 2021-02-09 | Establishment Labs S.A. | Textured surfaces for breast implants |
US11890179B2 (en) | 2014-02-17 | 2024-02-06 | Establishment Labs S.A. | Textured surfaces for breast implants |
US11026775B2 (en) | 2014-02-17 | 2021-06-08 | Establishment Labs S.A. | Textured surfaces for breast implants |
EP4098222A1 (en) | 2014-02-17 | 2022-12-07 | Establishment Labs S.A. | Textured surfaces for breast implants |
US20170281350A1 (en) * | 2014-07-17 | 2017-10-05 | Poriferous, LLC | Orbital Floor Sheet |
US20150320561A1 (en) * | 2014-07-17 | 2015-11-12 | Poriferous, LLC | Orbital Floor Sheet |
US10758355B2 (en) * | 2014-07-17 | 2020-09-01 | Poriferous, LLC | Orbital floor sheet |
US9724198B2 (en) * | 2014-07-17 | 2017-08-08 | Poriferous, LLC | Orbital floor sheet |
US10549015B2 (en) | 2014-09-24 | 2020-02-04 | Sofradim Production | Method for preparing an anti-adhesion barrier film |
US11202698B2 (en) | 2015-12-04 | 2021-12-21 | Establishment Labs S.A. | Textured surfaces for implants |
ES2681726R1 (en) * | 2015-12-29 | 2019-01-04 | Fundacion Tecnalia Res & Innovation | POROUS POLYMERIC ARTICLE OF UHMWPE, PROCESS FOR ITS PRODUCTION AND IMPLANT AND / OR FRAMEWORK MANUFACTURED FROM THEMSELVES |
WO2017114764A1 (en) * | 2015-12-29 | 2017-07-06 | Fundación Tecnalia Research & Innovation | Uhmwpe porous polymer article, process for its production and implant and/or scaffold made thereof |
US11857409B2 (en) | 2016-05-11 | 2024-01-02 | Establishment Labs Holdings, Inc. | Medical implants and methods of preparation thereof |
US11045307B2 (en) | 2016-05-11 | 2021-06-29 | Establishment Labs S.A. | Medical implants and methods of preparation thereof |
US10898181B2 (en) | 2017-03-17 | 2021-01-26 | Cypris Medical, Inc. | Suturing system |
US11213614B2 (en) * | 2017-03-20 | 2022-01-04 | The George Washington University | Vascularized biphasic tissue constructs |
EP3636292A4 (en) * | 2017-05-29 | 2021-03-03 | Educational Foundation Of Osaka Medical And Pharmaceutical University | Meniscus regeneration substrate |
CN110709111A (en) * | 2017-05-29 | 2020-01-17 | 学校法人大阪医科药科大学 | Meniscal regeneration substrate |
US11103236B2 (en) | 2018-04-06 | 2021-08-31 | Cypris Medical, Inc. | Suturing system |
US10660637B2 (en) | 2018-04-06 | 2020-05-26 | Cypris Medical, Inc. | Suturing system |
US11033261B2 (en) | 2018-05-31 | 2021-06-15 | Cypris Medical, Inc. | Suture system |
WO2019231478A1 (en) * | 2018-05-31 | 2019-12-05 | Cypris Medical, Inc. | Suture system |
US11717924B2 (en) | 2019-11-04 | 2023-08-08 | Covidien Lp | Devices, systems, and methods for treatment of intracranial aneurysms |
US11685007B2 (en) | 2019-11-04 | 2023-06-27 | Covidien Lp | Devices, systems, and methods for treatment of intracranial aneurysms |
US11679458B2 (en) | 2019-11-04 | 2023-06-20 | Covidien Lp | Devices, systems, and methods for treating aneurysms |
US11633818B2 (en) | 2019-11-04 | 2023-04-25 | Covidien Lp | Devices, systems, and methods for treatment of intracranial aneurysms |
Also Published As
Publication number | Publication date |
---|---|
US6852330B2 (en) | 2005-02-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6852330B2 (en) | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration | |
US8691259B2 (en) | Reinforced foam implants with enhanced integrity for soft tissue repair and regeneration | |
US20020127265A1 (en) | Use of reinforced foam implants with enhanced integrity for soft tissue repair and regeneration | |
US6599323B2 (en) | Reinforced tissue implants and methods of manufacture and use | |
AU783206B2 (en) | Attachment of absorbable tissue scaffolds to scaffold fixation devices | |
US10583220B2 (en) | Method and apparatus for resurfacing an articular surface | |
US8641775B2 (en) | Viable tissue repair implants and methods of use | |
EP1410811A1 (en) | Biocompatible scaffolds with tissue fragments |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: ETHICON, INC., NEW JERSEY Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:BOWMAN, STEVEN M.;BRUKER, IZI;REZANIA, ALIREZA;REEL/FRAME:011859/0549;SIGNING DATES FROM 20010409 TO 20010505 |
|
FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: LARGE ENTITY |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
FPAY | Fee payment |
Year of fee payment: 4 |
|
FPAY | Fee payment |
Year of fee payment: 8 |
|
AS | Assignment |
Owner name: DEPUY MITEK, LLC, MASSACHUSETTS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:ETHICON, INC.;REEL/FRAME:032203/0854 Effective date: 20140212 |
|
FPAY | Fee payment |
Year of fee payment: 12 |
|
AS | Assignment |
Owner name: DEPUY SYNTHES SALES, INC., MASSACHUSETTS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DEPUY MITEK, LLC;REEL/FRAME:048197/0069 Effective date: 20141229 Owner name: DEPUY SYNTHES PRODUCTS, INC., MASSACHUSETTS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DEPUY SYNTHES SALES INC.;REEL/FRAME:048197/0142 Effective date: 20141229 Owner name: DEPUY MITEK HOLDING CORPORATION, MASSACHUSETTS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DEPUY MITEK, LLC;REEL/FRAME:048197/0861 Effective date: 20141229 Owner name: DEPUY SYNTHES PRODUCTS, LLC, MASSACHUSETTS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DEPUY SPINE, LLC;REEL/FRAME:048198/0497 Effective date: 20141229 Owner name: DEPUY SYNTHES PRODUCTS, INC, MASSACHUSETTS Free format text: CHANGE OF NAME;ASSIGNOR:DEPUY SYNTHES PRODUCTS, LLC;REEL/FRAME:048198/0563 Effective date: 20141219 Owner name: SYNTHES USA, LLC, PENNSYLVANIA Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:DEPUY MITEK HOLDING CORPORATION;REEL/FRAME:048198/0860 Effective date: 20141219 Owner name: DEPUY SPINE, LLC, MASSACHUSETTS Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNOR:SYNTHES USA, LLC;REEL/FRAME:048829/0673 Effective date: 20141229 |